Background Efforts to reduce postoperative infections have garnered national attention, leading to practice guidelines for cardiac surgical perioperative care. The present study characterized the impact of health care–acquired infection (HAI) on index hospitalization costs and postdischarge health care utilization. Methods Adults undergoing elective coronary artery bypass graft surgery (CABG) or valve operations were identified in the 2016 to 2018 Nationwide Readmissions Database. Infections were categorized into bloodstream, gastrointestinal, pulmonary, surgical site, or urinary tract infections. Generalized linear or flexible hazard models were used to assess associations between infections and outcomes. Observed-to-expected ratios were generated to examine interhospital variation in HAI. Results Of an estimated 444,165 patients, 8% had HAI. Patients with HAI were older, had a greater burden of chronic diseases, and more commonly underwent CABG/valve or multivalve operations (all P<. 001). HAI was independently associated with mortality (odds ratio 4.02; 95% confidence interval [CI], 3.67 to 4.40), non-home discharge (odds ratio 3.48; 95% CI, 3.21 to 3.78), and a cost increase of $23,000 (95% CI, $20,900 to $25,200). At 90 days, HAI was associated with greater hazard of readmission (1.29; 95% CI, 1.24 to 1.35). Pulmonary infections had the greatest incremental impact on patient-level costs ($24,500; 95% CI, $23,100 to $26,000) and annual cohort costs ($121.8 million; 95% CI, $102.2 to $142.9 million). Significant hospital level variation in HAI was evident, with observed-to-expected ratios ranging from 0.17 to 4.30 for cases performed in 2018. Conclusions Infections after cardiac surgery remain common and are associated with inferior outcomes and increased resource use. Interhospital variation in this contemporary cohort emphasizes the ongoing need for systematic approaches in their prevention and management.