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Background: The effectiveness of simulation-based training of critical care nurses in sterile techniques has not been determined., Objective: To evaluate the effectiveness of simulation-based training of critical care nurses to use sterile techniques during central vein catheterization and the effect of such training on infection rates., Methods: A prospective controlled study with 12-month observational follow-up to assess the rate of catheter-related bloodstream infections in a 23-bed medical, surgical, neurological critical care unit., Results: Forty-six critical care nurses completed assessment and training in sterile technique skills in the simulation laboratory. Performance scores at baseline were poor: median scores in each category ranging from 0 to 2 out of a maximum score of 4 and a median total score of 7 out of a maximum score of 24. After simulation-based training, nurses' median scores in each ST category and their total scores improved significantly, with the median total score increasing to 23 (P < .01; median difference, 15; 95% CI, 14-16). After completion of the simulation-based training intervention, the mean infection rate in the unit was reduced by 85% from 2.61 to 0.4 infections per 1000 catheter-days (P = .02). The incidence rate-ratio derived from the Poisson regression (0.15; 95% CI, 0.03-0.78) indicates an 85% reduction in the incidence of catheter-related bloodstream infections in the unit after the intervention., Conclusion: Simulation-based training of critical care nurses in sterile technique is an important component in the strategy to reduce the occurrence of such infections and promote patient safety.