OBJECTIVE: To analyze patient risk factors and processes of care associated with secondary surgical-site infection (SSI) after coronary artery bypass grafting (CABG). METHODS: Data were collected prospectively between February and October 2010 for consenting adult patients undergoing CABG with saphenous vein graft (SVG) conduits. Patients who developed a deep or superficial SSI of the leg or groin within 65 days of CABG were compared with those who did not develop a secondary SSI. RESULTS: Among 2174 patients identified, 65 (3.0%) developed a secondary SSI. Median time to diagnosis was 16 days (interquartile range 11-29) with the majority (86%) diagnosed after discharge. Gram-positive bacteria were most common. Readmission was more common in patients with a secondary SSI (34% vs 17%, P < .01). After adjustment, an open SVG harvest approach was associated with an increased risk of secondary SSI (adjusted hazard ratio [HR], 2.12; 95% confidence interval [CI], 1.28-3.48). Increased body mass index (adjusted HR, 1.08, 95% CI, 1.04-1.12) and packed red blood cell transfusions (adjusted HR, 1.13; 95% CI, 1.05-1.22) were associated with a greater risk of secondary SSI. Antibiotic type, antibiotic duration, and postoperative hyperglycemia were not associated with risk of secondary SSI. CONCLUSIONS: Secondary SSI after CABG continues to be an important source of morbidity. This serious complication often occurs after discharge and is associated with open SVG harvesting, larger body mass, and blood transfusions. Patients with a secondary SSI have longer lengths of stay and are readmitted more frequently.