ABSTRACT: To determine the impact of surgical site infections (SSIs) on health care costs following common ambulatory surgical procedures throughout the cost distribution.Data on costs of SSIs following ambulatory surgery are sparse, particularly variation beyond just mean costs.We performed a retrospective cohort study of persons undergoing cholecystectomy, breast-conserving surgery, anterior cruciate ligament reconstruction, and hernia repair from December 31, 2004 to December 31, 2010 using commercial insurer claims data. SSIs within 90 days post-procedure were identified; infections during a hospitalization or requiring surgery were considered serious. We used quantile regression, controlling for patient, operative, and postoperative factors to examine the impact of SSIs on 180-day health care costs throughout the cost distribution.The incidence of serious and nonserious SSIs was 0.8% and 0.2%, respectively, after 21,062 anterior cruciate ligament reconstruction, 0.5% and 0.3% after 57,750 cholecystectomy, 0.6% and 0.5% after 60,681 hernia, and 0.8% and 0.8% after 42,489 breast-conserving surgery procedures. Serious SSIs were associated with significantly higher costs than nonserious SSIs for all 4 procedures throughout the cost distribution. The attributable cost of serious SSIs increased for both cholecystectomy and hernia repair as the quantile of total costs increased ($38,410 for cholecystectomy with serious SSI vs no SSI at the 70th percentile of costs, up to $89,371 at the 90th percentile).SSIs, particularly serious infections resulting in hospitalization or surgical treatment, were associated with significantly increased health care costs after 4 common surgical procedures. Quantile regression illustrated the differential effect of serious SSIs on health care costs at the upper end of the cost distribution.