Antimicrobial stewardship is one strategy to improve antibiotic use in order to reduce hospital-acquired infections. This article evaluates the impact of the AHRQ Safety Program for Improving Antibiotic Use, which helped more than 400 hospitals use an antibiotic stewardship program to implement and refine their policies regarding antibiotic use. The program led to a significant reduction in antibiotic use over the 1-year period and a 20% reduction in C. difficile infections. The approach encourages “self-stewardship,” in which front-line clinicians are empowered to improve their own antibiotic use in conjunction with traditional antibiotic stewardship programs.