To compare the costs associated with adjunctive azithromycin compared with standard cefazolin antibiotic prophylaxis alone for unscheduled and scheduled cesarean deliveries. METHODS: A decision analytic model was created to compare cefazolin alone with azithromycin plus cefazolin. Published incidences of surgical site infection after cesarean delivery were used to estimate the baseline incidence of surgical site infection in scheduled and unscheduled cesarean delivery using standard antibiotic prophylaxis. The effectiveness of adjunctive azithromycin prophylaxis was obtained from published randomized controlled trials for unscheduled cesarean deliveries. No randomized study of its use in scheduled procedures has been completed. Cost estimates were obtained from published literature, hospital estimates, and the Healthcare Cost and Utilization Project and considered costs of azithromycin and surgical site infections. A series of sensitivity analyses were conducted by varying parameters in the model based on observed distributions for probabilities and costs. The outcome was cost per cesarean delivery from a health system perspective. RESULTS: For unscheduled cesarean deliveries, cefazolin prophylaxis alone would cost $695 compared with $335 for adjunctive azithromycin prophylaxis, resulting in a savings of $360 (95% CI $155-451) per cesarean delivery. In scheduled cesarean deliveries, cefazolin prophylaxis alone would cost $254 compared with $111 for adjunctive azithromycin prophylaxis, resulting in a savings of $143 (95% CI 98-157) per cesarean delivery, if proven effective. These findings were robust to a multitude of inputs; as long as adjunctive azithromycin prevented as few as seven additional surgical site infections per 1,000 unscheduled cesarean deliveries and nine additional surgical site infections per 10,000 scheduled cesarean deliveries, adjunctive azithromycin prophylaxis was cost-saving. CONCLUSION: Adjunctive azithromycin prophylaxis is a cost-saving strategy in both unscheduled and scheduled cesarean deliveries.