To prospectively examine whether the association between tubal ligation, hysterectomy, unilateral oophorectomy, and ovarian cancer varied by patient, tumor, and surgical characteristics. Two prospective cohort studies (Nurses' Health Study and Nurses' Health Study II). Not applicable. A cohort of 121,700 married US female nurses, aged 30-55 years at baseline and another cohort of 116,430 US female nurses aged 25-42 years at baseline. We obtained data on gynecologic surgeries and ovarian cancer incidence through biennial questionnaires. We calculated hazard ratios (HRs) and 95% confidence intervals (CIs) adjusted for known and suspected ovarian cancer risk factors. Confirmed incident epithelial ovarian cancer. Overall, tubal ligation was associated with a decreased risk of ovarian cancer (HR, 0.76; 95% CI 0.64-0.90). The inverse association was stronger for nonserous tumors (HR, 0.57; 95% CI 0.40-0.82) and among women younger than 35 years at surgery (HR, 0.67; 95% CI 0.49-0.90). Hysterectomy was associated with a decreased risk of ovarian cancer (HR, 0.80; 95% CI 0.66-0.97) and was somewhat stronger for nonserous tumors (HR, 0.70; 95% CI 0.49-1.02). Unilateral oophorectomy was associated with a 30% lower risk (HR, 0.70; 95% CI 0.53-0.91), which did not differ by histologic subtype. Our study provides further support that tubal ligation reduces the risk of ovarian cancer, particularly for nonserous tumors and when conducted before the age of 35 years. The inverse association with hysterectomy, along with the stronger associations for nonserous tumors, supports shared biologic mechanisms for tubal ligation and hysterectomy.