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STUDY OBJECTIVE To quantify the relationship between type of benign pelvic disease and risk of surgical site infection (SSI) after hysterectomy. DESIGN Retrospective cohort study (Canadian Task Force classification II-2). SETTING Hospitals participating in the American College of Surgeons National Surgical Quality Improvement Program (NSQIP). PATIENTS Women who underwent hysterectomy from 2006-2015 and recorded in NSQIP database. INTERVENTION None. MEASUREMENTS AND MAIN RESULTS SSI risk was compared for type of benign pelvic disease, patient characteristics (i.e., age, race, and selected comorbidities) and process of care variables (i.e., admission status, type of hysterectomy, and operative time). SSI occurred in 2.48% of the 125,337 women who underwent hysterectomy. SSI was most frequent in patients with endometriosis and least frequent in those with genital prolapse (3.13% vs 1.39%; p <.0001). Following adjustment for potential confounders, the odds of SSI were higher in women undergoing hysterectomy for endometriosis (adjusted odds ratio [aOR], 1.79; 95% confidence interval [CI], 1.43- 2.25), uterine myomas (aOR, 1.28; 95% CI, 1.05-1.55), menstrual disorders (aOR, 1.46; 95% CI, 1.20-1.78), and pelvic pain (aOR, 1.75; 95% CI, 1.34-2.27) compared with women undergoing hysterectomy for genital prolapse. Other patient factors associated with SSI included age, body mass index, smoking, diabetes mellitus, chronic obstructive pulmonary disease, hypertension, and American Society of Anesthesiologists classification. Among process-of-care factors, inpatient status, route of hysterectomy, total vs subtotal hysterectomy, and operative time were also associated with SSI. CONCLUSION In addition to various patient and process-of-care factors known to be associated with SSI, type of underlying pelvic disease is an independent risk factor for SSI in women undergoing hysterectomy for benign indications.