Objectives: Asynchronous e-learning allows for targeted teaching, particularly advantageous when bedside and didactic education is insufficient. An asynchronous e-learning curriculum has not been studied across multiple centers in the context of a clinical rotation. We hypothesize that an asynchronous e-learning curriculum during the pediatric emergency medicine (EM) rotation improves medical knowledge among residents and students across multiple participating centers.Methods: Trainees on pediatric EM rotations at four large pediatric centers from 2012 to 2013 were randomized in a Solomon four-group design. The experimental arms received an asynchronous e-learning curriculum consisting of nine Web-based, interactive, peer-reviewed Flash/HTML5 modules. Postrotation testing and in-training examination (ITE) scores quantified improvements in knowledge. A 2 9 2 analysis of covariance (ANCOVA) tested interaction and main effects, and Pearson's correlation tested associations between module usage, scores, and ITE scores.Results: A total of 256 of 458 participants completed all study elements; 104 had access to asynchronous e-learning modules, and 152 were controls who used the current education standards. No pretest sensitization was found (p = 0.75). Use of asynchronous e-learning modules was associated with an improvement in posttest scores (p < 0.001), from a mean score of 18.45 (95% confidence interval [CI] = 17.92 to 18.98) to 21.30 (95% CI = 20.69 to 21.91), a large effect (partial g 2 = 0.19). Posttest scores correlated with ITE scores (r 2 = 0.14, p < 0.001) among pediatric residents.Conclusions: Asynchronous e-learning is an effective educational tool to improve knowledge in a clinical rotation. Web-based asynchronous e-learning is a promising modality to standardize education among multiple institutions with common curricula, particularly in clinical rotations where scheduling difficulties, seasonality, and variable experiences limit in-hospital learning.ACADEMIC EMERGENCY MEDICINE 2014;21:912-919