BACKGROUND AND OBJECTIVES: The Mexican Institute of Social Security (IMSS) is the largest public health care system in Mexico. IMSS family physicians' management of clinical problems is frequently not consistent with published evidence. This study aimed to evaluate the effects of a multifaceted educational intervention to improve management of acute respiratory infections (ARI) by IMSS family physicians. METHODS: A non-randomized pre-post intervention with comparison group design was conducted in eight IMSS family medicine clinics in which 106 family physicians practiced. An evidence-based clinical guideline for ARI management was developed, and clinical tutors were trained. The three-stage intervention comprised interactive workshops, individual tutorials, and round-table peer-review sessions. The main outcome was appropriate ARI case management. The intervention effect was calculated by using the differences-in-differences model, adjusting for cluster of physicians. RESULTS: In the intervention group, the difference in mean proportion of improvement compared with baseline evaluation was 22.6% (95% confidence interval [CI]=10.3 to 34.9) for appropriate prescription of antibiotics, 29.8% (95% CI=17.2 to 42.4) for indication of worsening signs, and 19.6% (95% CI=11.2 to 28.0) for overall appropriate case management. The comparison group showed no significant changes. CONCLUSIONS: The educational intervention improved ARI management. Further studies are needed to analyze organizational implications, cost, sustainability, and effects on health outcomes.