OBJECTIVE To determine if there is an association between oral contraceptive (OC) use and uterine fibroids. DESIGN Case-control study. SETTING University hospitals in Italy. SUBJECTS Cases were 843 women, aged < 55 (median 43, range 21-54) years, who were undergoing surgery between 1986 and 1997 for uterine fibroids diagnosed within the previous 2 years. Controls were 1557 age-matched women with an intact uterus, who were admitted to hospital for acute disorders that were not gynecological, hormonal or cancerous and who had no history of uterine fibroids. 87% of cases and 82% of controls were married, 98% and 80%, respectively, were premenopausal, and 31% and 24%, respectively, were nulliparous. INTERVENTION All women were interviewed while in hospital to obtain information on demographics, reproductive history, lifestyle factors, and OC use (at time of diagnosis for cases). MAIN OUTCOME MEASURES Odds ratio (OR, 95% CI) for uterine fibroids in women who used OC, compared to those who did not use OC, adjusted for other risk factors and calendar year. MAIN RESULTS 30% of cases and 23% of controls had used OC at some time and 2.0% and 3.5%, respectively, were current users. The OR for uterine fibroids was 1.1 (0.8-1.3) for ever-use of OC. The risk in ex-users was similar to that of non-users (OR 1.1, CI 0.9-1.4), but in current users the risk was significantly reduced (OR 0.3, CI 0.2-0.6). The odds ratio for fibroids decreased with increasing duration of ever-use: 1.4 (1.0-1.9) for 1 year or less of OC use, 1.0 (0.7-1.4) for 2-3 years, 0.8 (0.5-1.2) for 4-6 years, and 0.5 (0.3-0.9) for 7 years or more (P for trend 0.03). Time since last use had no effect on risk. CONCLUSION The use of oral contraceptives was not associated with an increased risk of uterine fibroids. The risk was significantly decreased in women who were current OC users and in those who had used OC for 7 years or more.