To determine the comparative effectiveness of technology-enhanced simulation, we summarized the results of studies comparing technology-enhanced simulation training with nonsimulation instruction for health professions learners. We systematically searched databases including MEDLINE, Embase, and Scopus through May 2011 for relevant articles. Working in duplicate, we abstracted information on instructional design, outcomes, and study quality. From 10,903 candidate articles, we identified 92 eligible studies. In random-effects meta-analysis, pooled effect sizes (positive numbers favoring simulation) were as follows: satisfaction outcomes, 0.59 (95% confidence interval, 0.36–0.81; n = 20 studies); knowledge, 0.30 (0.16–0.43; n = 42); time measure of skills, 0.33 (0.00–0.66; n = 14); process measure of skills, 0.38 (0.24–0.52; n = 51); product measure of skills, 0.66 (0.30–1.02; n = 11); time measure of behavior, 0.56 (−0.07 to 1.18; n = 7); process measure of behavior, 0.77 (−0.13 to 1.66; n = 11); and patient effects, 0.36 (−0.06 to 0.78; n = 9). For 5 studies reporting comparative costs, simulation was more expensive and more effective. In summary, in comparison with other instruction, technology-enhanced simulation is associated with small to moderate positive effects.