BACKGROUND The number of pediatric antimicrobial stewardship programs (ASPs) is increasing and program evaluation is a key component to improve efficiency and enhance stewardship strategies. OBJECTIVE To determine the antimicrobials and diagnoses most strongly associated with a recommendation provided by a well-established pediatric ASP. DESIGN AND SETTING Retrospective cohort study from March 3, 2008, to March 2, 2013, of all ASP reviews performed at a free-standing pediatric hospital. METHODS ASP recommendations were classified as follows: stop therapy, modify therapy, optimize therapy, or consult infectious diseases. A multinomial distribution model to determine the probability of each ASP recommendation category was performed on the basis of the specific antimicrobial agent or disease category. A logistic model was used to determine the odds of recommendation disagreement by the prescribing clinician. RESULTS The ASP made 2,317 recommendations: stop therapy (45%), modify therapy (26%), optimize therapy (19%), or consult infectious diseases (10%). Third-generation cephalosporins (0.20) were the antimicrobials with the highest predictive probability of an ASP recommendation whereas linezolid (0.05) had the lowest probability. Community-Acquired pneumonia (0.26) was the diagnosis with the highest predictive probability of an ASP recommendation whereas fever/neutropenia (0.04) had the lowest probability. Disagreement with ASP recommendations by the prescribing clinician occurred 22% of the time, most commonly involving community-Acquired pneumonia and ear/nose/throat infections. CONCLUSIONS Evaluation of our pediatric ASP identified specific clinical diagnoses and antimicrobials associated with an increased likelihood of an ASP recommendation. Focused interventions targeting these high-yield areas may result in increased program efficiency and efficacy. Infect Control Hosp Epidemiol 2015;00(0): 1-8.