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To determine whether simulation training of ultrasound (US)-guided central venous catheter (CVC) insertion skills on a partial task trainer improves cannulation and insertion success rates in clinical practice.This prospective, randomized, controlled, single-blind study of first- and second-year residents occurred at a tertiary care teaching hospital from January 2007 to September 2008. The intervention group (n = 90) received a didactic and hands-on, competency-based simulation training course in US-guided CVC insertion, whereas the control group (n = 95) received training through a traditional, bedside apprenticeship model. Success at first cannulation and successful CVC insertion served as the primary outcomes. Secondary outcomes included reduction in technical errors and decreased mechanical complications.Blinded independent raters observed 495 CVC insertions by 115 residents over a 21-month period. Successful first cannulation occurred in 51% of the intervention group versus 37% of the control group (P = .03). CVC insertion success occurred for 78% of the intervention group versus 67% of the control group (P = .02). Simulation training was independently and significantly associated with success at first cannulation (odds ratio: 1.7; 95% confidence interval: 1.1–2.8) and with successful CVC insertion (odds ratio: 1.7; 95% confidence interval: 1.1–2.8)—both independent of US use, patient comorbidities, or resident specialty. No significant differences related to technical errors or mechanical complications existed between the two groups.Simulation training was associated with improved in-hospital performance of CVC insertion. Procedural simulation was associated with improved residents' skills and was more effective than traditional training.