Although widely used in clinical practice, long peripheral (LPCs) and midline catheters (MCs) are often misclassified because of their similar characteristics. Comparative studies on these devices are lacking. This study aimed to explore complications risks in polyurethane LPCs and MCs. Prospective cohort study. Catheter-failure within 30days was the primary outcome, catheter-related bloodstream infection (CR-BSI), thrombosis, and fibroblastic sleeve were secondary outcomes. The average number of drugs infused per day was computed to measure the overall intensity of catheters' use. The catheter-failure incidence was 5.7 and 3.4/1,000 catheter-days for LPCs and MCs, respectively. MCs were associated with an adjusted lower risk of catheter-failure (hazard ratio 0.311,95% confidence interval 0.106-0.917,P=.034). The daily number of drugs infused was higher for MCs (P<.001) and was associated witha greater risk catheter-failure risk (P=.021). Sensitivity analysis showed a decreased catheter-failure risk for MCs starting from day-10 from positioning. The incidence of CR-BSI (0.9 vs 0.0/1,000 catheter-days), thrombosis (8.7 vs 3.5/1,000 catheter-days), and fibroblastic sleeve (14.0 vs 8.1/1,000 catheters-days) was higher for LPCcatheters. Despite more intensive drug administration, MCs were associated with a longer uncomplicated indwelling time.