OBJECTIVE: Evaluate the effects of handshake stewardship on adult general surgical units. DESIGN: Retrospective quasi-experimental pre- and post-intervention study. SETTING: A total of 1,278 bed academic medical center with a level 1 trauma center in St. Louis, Missouri. PATIENTS: Adults admitted to general surgery units. INTERVENTION: Once weekly handshake antimicrobial stewardship rounds were initiated in January 2022 on adult general surgery units. The handshake stewardship team consisted of an infectious diseases (ID) physician and pharmacist who reviewed charts of patients receiving systemic antimicrobials without a formal ID consult. Antimicrobial recommendations were delivered in person to general surgery teams including trauma, geriatric trauma, and emergency/general surgery. RESULTS: A total of 1,241 charts were reviewed during the post-implementation period with 391 interventions. Seventy-two percent of those interventions were accepted and the acceptance rate improved over the 18-month post-implementation period. Total antimicrobial usage significantly decreased between the pre- and post-implementation period (608 vs 542 d of therapy/1,000 d present, CONCLUSION: A once-weekly handshake antimicrobial stewardship program was successfully implemented in general surgery units. Antimicrobial use significantly decreased without negatively impacting hospital mortality.