Surgical site infections (SSI) are one of the most common and costly hospital-acquired infections in the United States. Meteorological variables such as temperature, humidity, and precipitation may represent a neglected group of risk factors for SSI. Using a national private insurance database, we collected admission and follow-up records for National Healthcare Safety Network-monitored surgical procedures and associated climate conditions from 2007 to 2014. We found that every 10 cm increase of maximum daily precipitation resulted in a 1.09 odds increase in SSI after discharge, while every g/kg unit increase in specific humidity resulted in a 1.03 odds increase in SSI risk after discharge. We identified the Southeast region of the United States at highest risk of climate change-related SSI, with an estimated 3% increase in SSI by 2060 under high emission assumptions. Our results describe the effect of climate on SSI and the potential burden of climate-change related SSI in the United States.