Background Peripheral intravenous catheters (PVCs) are essential to modern healthcare and are the most frequently used vascular access device. They provide a quick, simple, and cost-effective method to gain vascular access, and up to 70% of hospitalised patients will receive at least one PVC during their admission; a large proportion of these are inserted by registered nurses. PVCs however frequently develop complications associated with their insertion and use which result in catheter failure. PVC failure interrupts important intravenous (IV) treatment, such as antibiotics or chemotherapy, and may result in longer hospital stays and increased healthcare costs. Evidence-based nursing practice is vital for the prevention of PVC complications and failure. Aims and objectives The overarching aim of this research was to identify effective methods to prevent PVC failure. There were two objectives to guide the two research phases: 1) to determine modifiable risk factors associated with PVC failure and complications; and 2) to evaluate the feasibility of large randomised controlled trial (RCT) of a vascular access specialist versus a generalist PVC inserter model to prevent PVC failure. Design This research was underpinned by the Medical Research Council Framework for the Evaluation of Complex Interventions and consisted of two study phases: a multivariate regression analysis of an existing large dataset; and a pilot randomised control trial comparing the generalist inserter with a vascular access specialist for PVC placement. A systematic review with meta-analysis on PVC failure and a critical review of literature evaluating the effectiveness of a specialist versus a generalist PVC inserter model to prevent failure were also undertaken to clearly identify the compelling need for the arch. Phase 1 Setting: Medical and surgical wards of a Queensland tertiary hospital Sample: Adult patients requiring a PVC Measurements: Demographic, clinical, and potential PVC risk factors had been collected for a prospective cohort study. Failure outcomes were noted if the catheter had complications at removal. Main Result Data from 1,000 patients were analysed. Catheter failure occurred in 512 (32%) of 1578 PVCs. Occlusion/infiltration risk factors were: IV flucloxacillin [Hazard Ratio (HR) 1.98, 95% confidence interval (CI) [1.19–3.31], 22-gauge PVCs [HR 1.43, 95% CI 1.02–2.00], and female patients [HR 1.48, 95% CI 1.10–2.00]. Phlebitis was associated with: female patients [HR 1.81, 95% CI 1.40–2.35], bruised insertion sites [HR 2.16, 95% CI 1.26–3.71], IV flucloxacillin [HR 2.01, 95% CI 1.26–3.21], and dominant side insertion [HR 1.39, 95% CI 1.09–1.77]. Dislodgement risks were a paramedic insertion [HR 1.78, 95% CI 1.03–3.06]. Each increase by 1 in the average number of daily PVC accesses was associated [HR 1.1, 95% CI 1.03–1.20]–[HR 1.14, 95% CI 1.08–1.21] with occlusion/infiltration, phlebitis and dislodgement. Additional securement products were associated with less [HR 0.32, 95% CI 0.22–0.46]–[HR 0.63, 95% CI 0.48–0.82] occlusion/infiltration, phlebitis and dislodgement. Phase 2 Setting: Medical and surgical wards of a Queensland tertiary hospital Sample: 138 patients who were over the age of 18 and required a PVC for greater than 24 hours. Study Design: Single-centre, parallel-group, pilot RCT Interventions: Participants were randomised to have their PVC inserted by either:  a Vascular Access Specialist (VAS), who for this trial was a member of an intravenous therapy team for over 20 years as well as a hospital and university educator of clinicians to place PVCs; or  generalist inserters, who were accredited PVC inserters who placed the catheter as per usual hospital policy. Primary and secondary outcomes Feasibility outcomes were achieved: 92% of screened patients were eligible; two patients refused participation; there was no attrition or missing outcome data. PVC failure was higher with generalists 27/50 (54%) than for VAS 33/69 (48%) [228 vs 217 per 1000 PVC days; Incidence Rate Ratio 1.05, 95% CI 0.61–1.80]. There were no local or PVC-related infections in either group. All PVCs (n = 69) were successfully inserted in the VAS group. In the generalist group, 19 (28%) patients did not have a PVC inserted. There was inadequate data available for the cost-effectiveness analysis, but the mean insertion procedure time was two minutes in the VAS group and 11 minutes in the generalist group. Overall satisfaction with the PVC was measured on an 11-point scale (0 = not satisfied and 10 = satisfied) and higher in the VAS group (n = 43; median = 7) compared to the generalist group (n = 20; median = 4.5). The multivariable model identified medical diagnosis and bed-bound status as significantly associated with higher PVC failure, and securement with additional non-sterile tape was significantly associated with lower PVC failure. Conclusion This PhD research has revealed the high rate of PVC failure in acute care hospitals, and extends existing evidence related to PVC failure and identified modifiable risk factors. These results, which include several newly identified risk factors for PVC failure, will inform education programs to improve inserter skill development and clinician management of PVCs to reduce catheter failure. The PhD work has confirmed the feasibility and need for a large, multi-centre RCT to test PVC insertion models and provides the first randomised data to support the VAS model as preferable to the generalist inserter model. PVC failure is a significant worldwide problem which, until now, appears unacknowledged and unaddressed. Effective nursing interventions and a strong evidence base for practice are vital for preventing poor outcomes for patients with PVCs. This PhD research identifies areas for improvement, and an urgent health system and professional response is needed.