BACKGROUND AND OBJECTIVES: Simulation-based education strategies to teach regional anesthesia have been described, but their efficacy largely has been assumed. We designed this study to determine whether residents trained using the simulation-based strategy of deliberate practice show greater improvement of ultrasound-guided regional anesthesia (UGRA) skills than residents trained using self-guided practice in simulation. METHODS: Anesthesiology residents new to UGRA were randomized to participate in either simulation-based deliberate practice (intervention) or self-guided practice (control). Participants were recorded and assessed while performing simulated peripheral nerve blocks at baseline, immediately after the experimental condition, and 3 months after enrollment. Subject performance was scored from video by 2 blinded reviewers using a composite tool. The amount of time each participant spent in deliberate or self-guided practice was recorded. RESULTS: Twenty-eight participants completed the study. Both groups showed within-group improvement from baseline scores immediately after the curriculum and 3 months following study enrollment. There was no difference between groups in changed composite scores immediately after the curriculum (P = 0.461) and 3 months following study enrollment (P = 0.927) from baseline. The average time in minutes that subjects spent in simulation practice was 6.8 minutes for the control group compared with 48.5 minutes for the intervention group (P < 0.001). CONCLUSIONS: In this comparative effectiveness study, there was no difference in acquisition and retention of skills in UGRA for novice residents taught by either simulation-based deliberate practice or self-guided practice. Both methods increased skill from baseline; however, self-guided practice required less time and faculty resources.