INTRODUCTION: Peripheral intravenous cannulation (PIVC) insertion is challenging for some patients, leading to delays in care and workflow. A few easy-to-identify risk factors can differentiate difficult to cannulate (DIVA) patients. METHODS: A prospective observational study of adults undergoing PIVC was undertaken. Nursing and medical staff inserted PIVC using their usual practices. Patient, PIVC characteristics, number of attempts and staff characteristics were captured. Indicators of high-risk-for-DIVA were: no vein seen, and/or no vein palpable, and/or a history of difficult PIVC. The experience and outcomes for high-risk-for-DIVA patients were compared to non-DIVA. RESULTS: 1084 adults with PIVCs inserted were observed; with (378 (34.9%)) qualifying as high-risk-for-DIVA. First attempt success was achieved for 831 (76.7%) patients overall, with high-risk-for-DIVA significantly less likely to require one attempt (61.1% vs 85.0%, p < 0.001). High-risk-for-DIVA were more likely to have: PIVC aborted, multiple attemptors, ultrasound -guidance, smaller gauge PIVC, and wrist or hand placement. CONCLUSION: Simple predictors for difficult PIVC are known, and were present in about one-third of adults in this cohort. Earlier identification and escalation of these patients to more experienced cannulators, those experienced with US, and/or placement in the wrist/hand with a small gauge PIVC, may assist in avoiding unnecessary cannulation attempts and delays.