We examined patient and surgical factors associated with deep surgical site infection (SSI) following total hip replacement (THR) in a large integrated healthcare system. A retrospective review of a cohort of primary THRs performed between 2001 and 2009 was conducted. Patient characteristics, surgical details, surgeon and hospital volumes, and SSIs were identified using the Kaiser Permanente Total Joint Replacement Registry (TJRR). Proportional-hazard regression models were used to assess risk factors for SSI. The study cohort consisted of 30,491 THRs, of which 17,474 (57%) were performed on women. The mean age of the patients in the whole series was 65.5 years (13 to 97; SD 11.8) and the mean body mass index was 29.3 kg/m(2) (15 to 67; SD 5.9). The incidence of SSI was 0.51% (155 of 30,491). Patient factors associated with SSI included female gender, obesity, and American Society of Anesthesiologists (ASA) score ≥ 3. Age, diagnosis, diabetes and race were not associated with SSI. The only surgical factor associated with SSI was a bilateral procedure. Surgeon and hospital volumes, use of antibiotic-laden cement, fixation method, laminar flow, body exhaust suits, surgical approach and fellowship training were not associated with risk of SSI. A comprehensive infection surveillance system, combined with a TJRR, identified patient and surgical factors associated with SSI. Obesity and chronic medical conditions should be addressed prior to THR. The finding of increased SSI risk with bilateral THR requires further investigation.