Abstract Antibiotic overuse is common in ambulatory care settings, underscoring the importance of outpatient antibiotic stewardship to ensure safe and effective antibiotic prescription. In response to this need, the Agency for Healthcare Research and Quality (AHRQ) developed the AHRQ Safety Program for Improving Antibiotic Use in Ambulatory Care. The Safety Program successfully assisted 389 outpatient practices across the United States to establish ambulatory antibiotic stewardship. Herein, we have used lessons learned from the AHRQ Safety Program to describe a step-by-step framework to assist practices with establishing antibiotic stewardship in the outpatient setting. Steps include obtaining support from practice leadership; establishing an antibiotic stewardship team; garnering support from practice members; determining how to access antibiotic prescribing data; building communication skills around antibiotic use in the practice; implementing educational content around an infectious syndrome; monitoring antibiotic prescription data; and implementing a sustainability plan.