Abstract: Objective To evaluate the efficacy and metabolic safety of long-term treatment with ethinyl oestradiol/cyproterone and desogestrel/ethinyl oestradiol tablets in women with polycystic ovary syndrome (PCOS). Method Women with PCOS from West China Second Hospital of Sichuan University enrolled between September, 2011 and August, 2013 were randomly allocated to receive either ethinyl oestradiol/cyproterone tablets (Group A, n=355) or desogestrel/ethinyl oestradiol tablets (Group B, n=357) for a prospective observation period of 6 months. Women with insulin resistance also received metformin. At baseline, 3 months, and 6 months, the patients were evaluated for menstruation, acne score, body mass index (BMI), waist-tohip ratio (WHR), plasma levels of sex hormones, fasting blood glucose (FPG), HOMA-insulin resistance index (HOMA-IR), serum lipid, ovarian volume, and the number of ovarian follicles. Results All the patients had a regular menstrual cycle after treatments. Testosterone level, acne score, LH/FSH, ovarian volume, and the number of follicles decreased significantly after the treatments without significant differences between the two groups. Significant increases were noted in TG, TCh, LDL, HDL, and AIP, and HDL level in group A as compared with group B (P<0.001). FPG decreased in both groups, and was significantly lower in group B at 6 months (P<0.05). BMI and WHR decreased in all the patients with insulin resistance after combination treatment with metformin (P<0.05), but increased significantly in patients without insulin resistance (P<0.05). In group A, HOMA- IR significantly increased in patients without insulin resistance at 3 months (P<0.05), whereas a significant increase was not observed until 6 months in group B (P<0.05). Conclusion Both ethinyl oestradiol/ cyproterone tablets and desogestrel/ethinyl oestradiol tablets can relieve the symptoms of PCOS, but it is advisable to assess the risk of cardiovascular disease before the treatments.