A total of 117,935 patients were identified (45,612 undergoing total hip arthroplasty and 72,323 undergoing total knee arthroplasty). Of these, 402 (0.34%) developed sepsis following surgery. Patients who developed sepsis had an elevated mortality rate (3.7% vs 0.1%, P < .001). Among the 402 patients who developed sepsis, 124 (31%) had concomitant UTI, 110 (27%) SSI, and 60 (15%) pneumonia. Twenty-one patients (5%) had multiple infectious sources and 129 patients (32%) had no identifiable source. Independent risk factors for sepsis included greater age, male sex, functional dependence, insulin-dependent diabetes, hypertension, chronic obstructive pulmonary disease, current smoker, and greater operative time.