IMPORTANCE Resuscitation training programs use simulation and debriefing as an educational modality with limited standardization of debriefing format and content. Our study attempted to address this issue by using a debriefing script to standardize debriefings. OBJECTIVE To determine whether use of a scripted debriefing by novice instructors and/or simulator physical realism affects knowledge and performance in simulated cardiopulmonary arrests. DESIGN Prospective, randomized, factorial study design. SETTING The study was conducted from 2008 to 2011 at 14 Examining Pediatric Resuscitation Education Using Simulation and Scripted Debriefing (EXPRESS) network simulation programs. Interprofessional health care teams participated in 2 simulated cardiopulmonary arrests, before and after debriefing. PARTICIPANTS We randomized 97 participants (23 teams) to nonscripted low-realism; 93 participants (22 teams) to scripted low-realism; 103 participants (23 teams) to nonscripted high-realism; and 94 participants (22 teams) to scripted high-realism groups. INTERVENTION Participants were randomized to 1 of 4 arms: permutations of scripted vs nonscripted debriefing and high-realism vs low-realism simulators. MAIN OUTCOMES AND MEASURES Percentage difference (0%-100%) in multiple choice question (MCQ) test (individual scores), Behavioral Assessment Tool (BAT) (team leader performance), and the Clinical Performance Tool (CPT) (team performance) scores postintervention vs preintervention comparison (PPC). RESULTS There was no significant difference at baseline in nonscripted vs scripted groups for MCQ (P = .87), BAT (P = .99), and CPT (P = .95) scores. Scripted debriefing showed greater improvement in knowledge (mean [95% CI] MCQ-PPC, 5.3% [4.1%-6.5%] vs 3.6% [2.3%-4.7%]; P = .04) and team leader behavioral performance (median [interquartile range (IQR)] BAT-PPC, 16% [7.4%-28.5%] vs 8% [0.2%-31.6%]; P = .03). Their improvement in clinical performance during simulated cardiopulmonary arrests was not significantly different (median [IQR] CPT-PPC, 7.9% [4.8%-15.1%] vs 6.7% [2.8%-12.7%], P = .18). Level of physical realism of the simulator had no independent effect on these outcomes. CONCLUSIONS AND RELEVANCE The use of a standardized script by novice instructors to facilitate team debriefings improves acquisition of knowledge and team leader behavioral performance during subsequent simulated cardiopulmonary arrests. Implementation of debriefing scripts in resuscitation courses may help to improve learning outcomes and standardize delivery of debriefing, particularly for novice instructors.