Objective: Our objective was to examine the impact of a human factor-designed multimodal intervention on the proportion of unused peripheral i.v. cannula (PIVC) insertion in our ED. Methods: A pre- and post-multimodal intervention retrospective cohort study was conducted using a structured electronic medical record review within a single adult tertiary ED in Australia. Pre-intervention data was collected 30 days prior to the multimodal intervention, with 30 day post-intervention data collected 3 months after the intervention commenced. The rates of PIVC inserted, the unused rate and the unused but appropriately inserted cannulas were the main outcome measures. Results: Intravenous cannula insertion rates decreased by 12.9% (95% confidence interval [CI] 12.19–13.61) between the pre-intervention (1413/4167 [33.9%]; 95% CI 32.5–35.4) and post-intervention cohort (928/4421 [21.0%]; 95% CI 19.8–22.2). An analysis of 754 cases (376 pre-intervention and 378 post-intervention) showed that 139 of 376 (37.0%; 95% CI 32.1–42.1) i.v. cannulas were unused pre-intervention, while 73 of 378 (19.3%; 95% CI 15.4–23.7) was unused post-intervention; an absolute reduction of 17.7% (95% CI 14.98–20.42). The relative risk of an unused i.v. cannula was 0.52 (95% CI 0.41–0.67). The proportion of unused but appropriately inserted i.v. cannulas remained unchanged in both cohorts, with a relative risk of 0.91 (95% CI 0.58–1.42). Conclusion: Our multimodal intervention successfully reduced the number of unused PIVCs inserted in the ED, with a reduction in overall and unused PIVC insertions without any change in appropriate insertions.