To estimate trends in patient characteristics and obstetric complications in an 8-year cohort of patients undergoing cesarean delivery and to use time series analysis to estimate the effect of infection prevention interventions and secular trends in patient characteristics on postcesarean delivery surgical site infections. A multivariable autoregressive integrated moving average model was used to perform time series analysis on a 96-month retrospective cohort of patients who underwent cesarean delivery (January 2003-December 2010) in a U.S. tertiary care hospital. We identified 8,668 women who underwent cesarean delivery. Median age was 26 years (range 12-53 years), 3,093 (35.7%) of patients had body mass indexes (BMIs) of 35 or greater, 2,561 (29.5%) were of white race, and 303 (3.5%) had a surgical site infection. Over the study period, there was a significant increase in the proportion of patients who underwent cesarean delivery who had BMIs of 35 or higher, hypertension or mild preeclampsia, and severe preeclampsia or eclampsia. A nonseasonal autoregressive integrated moving average model with a linear trend and no autocorrelation was identified. In the multivariable autoregressive integrated moving average model of postcesarean surgical site infections, implementation of a policy to administer prophylactic antibiotics within 1 hour before incision, instead of at the time of cord clamp, led to a 48% reduction in cesarean delivery surgical site infections (Δ=−5.4 surgical site infections per 100 cesarean deliveries; P<.001). A change in policy to administer prophylactic antibiotics before incision resulted in a significant reduction in postcesarean surgical site infections. III.