- Objective: To investigate a possible linkage between the use of fertility drugs for infertility and the risk of breast and ovarian cancers. Design: Long-term, historic-prospective study. Setting: Fertility clinic in a university hospital. Patient(s): Files of 1,197 infertile women with a mean (± SD) follow-up of 17.9 ± 5 years (21,407 person-years) were reviewed. Diagnoses, number of courses, and dosage of fertility drugs were extracted from the files. Intervention(s): Cancers were identified by record linkage to the National Cancer Registry. Histopathologic reports and data on estrogen and progesterone receptors in breast cancer tissue were also reviewed. Main Outcome Measure(s): Standardized incidence ratio with 95% confidence interval (CI) were used for risk assessment. Result(s): Of 20 breast cancers (standardized incidence ratio, 1.40 [95% CI, 0.83–2.10]), 16 were detected among 780 women who had been exposed to 3,978 cycles of clomiphene citrate (CC) and/or hMG (standardized incidence ratio, 1.65 [95% CI, 0.94–2.68]). The standardized incidence ratio for this cancer was significantly increased only in patients with one or two CC treatments and a dose of ≤1,000 mg (2.6 [1.19–5.0] and 2.52 [1.21–4.64], respectively). Two cases of ovarian cancer (1 patient unexposed) were observed with no evidence of excessive risk. Six of the eight patients with data on estrogen and progesterone receptors were exposed to CC, and all tested positive for these receptors. Conclusion(s): An association between the use of fertility drugs and an increased risk of breast and ovarian cancers has not been confirmed.