The occurrence of wound infections following cardiothoracic surgery has significant implications. However, the epidemiology of all chest and leg wound infections is infrequently described, and the effects on morbidity, mortality, and cost of care remain undefined. We identified 182 superficial and deep chest and leg infections in 163 patients following 1,554 coronary artery bypass graft (CABG), valve, and CABG/valve procedures over 30 months. The overall infection rate was 11.7%; infections of specific sites involved in the 1,554 procedures occurred at the following rates: 3.1%, superficial chest wounds; 2.3%, deep chest wounds; 4.6%, superficial leg wounds; and 2.2%, deep leg wounds. Chest infection rates were similar for all procedures. Multiple infections occurred in 9.8% of patients and were associated with female sex, diabetes, and prolonged surgery (P < .05). Purulent drainage and fever were more common in chest infections; erythema and pain were more common in leg infections (P < .05). Staphylococcus aureus (32.9%), coagulase-negative staphylococci (27.4%), and Enterobacteriaceae (26.0%) were identified most commonly. Enterobacteriaceae were more commonly isolated from leg wounds (P < .05). Adverse outcomes included reexploration (20.9%), flap surgery (12.3%), and death (4.3%). All adverse outcomes were more commonly associated with deep chest infections (P < .05), but superficial chest and leg infections also had a substantial impact on cardiothoracic surgery-related morbidity. Studies are needed to define site-specific risk factors so that the full potential of prevention and control measures can be realized.