Objective. To determine the natural history of simple unilocular adnexal cysts in asymptomatic postmenopausal women. Methods. Eight thousand seven hundred ninety-four asymptomatic postmenopausal women underwent transvaginal ultrasound as part of routine gynecological check-up at our institution between January 1995 and June 2002. All patients in whom a simple unilocular adnexal cyst was found out were offered surgical treatment or conservative follow-up with serial transvaginal ultrasound at 6-month intervals. In all these cases, serum CA-125 levels was determined. Results. Two hundred twenty-three simple adnexal cysts in 215 women were found out (prevalence: 2.5%). Annual incidence did not change significantly. Sixty-six (30.6%) women were lost after initial diagnosis. One hundred and forty-nine patients with 153 cysts were entered ultimately in the study. Forty-five (30%) underwent surgery (34 after initial diagnosis and 11 during follow-up). A total of 49 cysts were removed. The most frequent histological diagnosis was serous cystadenoma (84%). There was a case of a stage IA ovarian carcinoma (2% of the cysts removed, 0.6% of all the cysts included in the study). One hundred and four patients with 104 cysts underwent conservative follow-up throughout the study period. Forty-six (44%) of these cysts resolved spontaneously (74% of them within 2 years). In 14 (30%) of these women, a new cyst was diagnosed when follow-up went on. In 58 patients, cysts persisted during all study period (median follow-up: 48 months, range: 6-90 months), 69.6% of them remained unchanged, 17.2% increased, and 17.2% decreased. Patients in whom cysts resolved spontaneously had a shorter menopausal time (P = 0.001) and tend to be younger (P = 0.06). No differences were found regarding cysts' features. Conclusion. The risk of malignancy of simple adnexal cysts in asymptomatic postmenopausal women is low. Almost half of them will resolve spontaneously during follow-up. Most of those that persist remain unchanged. Asymptomatic postmenopausal women having simple adnexal cysts can be managed conservatively with a very reasonable degree of reassurance. © 2004 Elsevier Inc. All rights reserved.