Objective. To assess the relative importance of independent risk factors for peripheral intravenous catheter (PIVC) failure. Methods. Secondary data analysis from a randomized controlled trial of PIVC dwell time. The Prentice, Williams, and Peterson statistical model was used to identify and compare risk factors for phlebitis, occlusion, and accidental removal. Setting. Three acute care hospitals in Queensland, Australia. Participants. The trial included 3,283 adult medical and surgical patients (5,907 catheters) with a PIVC with greater than 4 days of expected use. Results. Modifiable risk factors for occlusion included hand, antecubital fossa, or upper arm insertion compared with forearm (hazard ratio [HR], 1.47 [95% confidence interval (CI), 1.28-1.68], 1.27 [95% CI, 1.08-1.49], and 1.25 [95% CI, 1.04-1.50], respectively); and for phlebitis, larger diameter PIVC (HR, 1.48 [95% CI, 1.08-2.03]). PIVCs inserted by the operating and radiology suite staff had lower occlusion risk than ward insertions (HR, 0.80 [95% CI, 0.67-0.94]). Modifiable risks for accidental removal included hand or antecubital fossa insertion compared with forearm (HR, 2.45 [95% CI, 1.93-3.10] and 1.65 [95% CI, 1.23-2.22], respectively), clinical staff insertion compared with intravenous service (HR, 1.69 [95% CI, 1.30-2.20]); and smaller PIVC diameter (HR, 1.29 [95% CI, 1.02-1.61]). Female sex was a nonmodifiable factor associated with an increased risk of both phlebitis (HR, 1.64 [95% CI, 1.28-2.09]) and occlusion (HR, 1.44 [95% CI, 1.30-1.61]). Conclusions. PIVC survival is improved by preferential forearm insertion, selection of appropriate PIVC diameter, and insertion by intravenous teams and other specialists.