OBJECTIVE To determine whether the seasonality of surgical site infections (SSIs) can be explained by changes in temperature. DESIGN Retrospective cohort analysis. SETTING The National Inpatient Sample database. PATIENTS All hospital discharges with a primary diagnosis of SSI from 1998 to 2011 were considered cases. Discharges with a primary or secondary diagnoses of specific surgeries commonly associated with SSIs from the previous and current month served as our "at risk" cohort. METHODS We modeled the national monthly count of SSI cases both nationally and stratified by region, sex, age, and type of institution. We used data from the National Climatic Data Center to estimate the monthly average temperatures for all hospital locations. We modeled the odds of having a primary diagnosis of SSI as a function of demographics, payer, location, patient severity, admission month, year, and the average temperature in the month of admission. RESULTS SSI incidence is highly seasonal, with the highest SSI incidence in August and the lowest in January. During the study period, there were 26.5% more cases in August than in January (95% CI, 23.3-29.7). Controlling for demographic and hospital-level characteristics, the odds of a primary SSI admission increased by roughly 2.1% per 2.8°C (5°F) increase in the average monthly temperature. Specifically, the highest temperature group, >32.2°C (>90°F), was associated with an increase in the odds of an SSI admission of 28.9% (95% CI, 20.2-38.3) compared to temperatures <4.4°C (<40°F). CONCLUSIONS At population level, SSI risk is highly seasonal and is associated with warmer weather. Infect Control Hosp Epidemiol 2017;38:809-816.