Background Simulation-based learning is a common educational tool in heath care training and frequently involves instructional designs based on Experiential Learning Theory (ELT). However, little research explores the effectiveness and efficiency of different instructional design methodologies appropriate for simulations. The aim of this study was to compare 2 instructional design models, ELT and Guided Experiential Learning (GEL), to determine which is more effective for training the central venous catheterization procedure. Methods Using a quasi-experimental randomized block design, nurse anesthetists completed training under 1 of the 2 instructional design models. Performance was assessed using a checklist of cnetral venous catheterization performance, pass rates, and critical action errors. Results Participants in the GEL condition performed significantly better than those in the ELT condition of the overall checklist score after controlling for individual practice time (F[1, 29] = 4.021, P = .027, Cohen's d = .71), had higher pass rates (P = .006, Cohen's d = 1.15), and had lower rates of failure due to critical action errors (P = .038, Cohen's d = .81).