This single centre randomized controlled trial was undertaken to compare the efficacy and safety of clomiphene citrate and low-dose recombinant FSH as first line pharmacological therapy for anovulatory infertility associated with polycystic ovary syndrome (PCOS). Seventy-six infertile patients with PCOS were randomized to receive clomiphene citrate (50-150 mg/day for 5 days) (clomiphene citrate group, n = 38) or recombinant human FSH (FSH group, n = 38) in a chronic, low-dose, step-up protocol (daily starting dose 75 IU) for up to three consecutive cycles. Ovarian response was monitored by transvaginal ultrasonography and human chorionic gonadotrophin (HCG) was given to trigger ovulation in all cycles with appropriate follicular development. The primary outcome measure was cumulative pregnancy after undergoing up to three treatment cycles. Secondary outcomes were cycle cancellation rate, ovulation rate per cycle, cumulative ovulation rate, pregnancy rate per cycle, incidence of OHSS, cumulative live birth rate, and multiple birth rate. One hundred and four clomiphene citrate cycles and 91 FSH cycles were evaluable. The relative risk and its 95% confidence interval were 1.17 (0.97-1.46) for HCG cycles with ovulation, 1.78 (0.92-3.54) for the pregnancy rate per woman, and 1.83 (0.79-4.40) for live births per woman in favour of FSH. The cumulative pregnancy rate after three treatment cycles was 43% with FSH and 24% with clomiphene citrate (P = 0.06). By logistic regression analysis, the factors predicting ovulation included female age, serum androstenedione and use of FSH. Predictors of pregnancy were duration of infertility and use of FSH. This randomized controlled trial suggests that low-dose recombinant FSH may be an effective alternative to clomiphene citrate in first-line treatment for anovulatory PCOS patients. Thus, further studies, possibly multi-centre, in order to avoid problems with patient recruitment, are warranted to confirm these results.