Introduction Polycystic ovary syndrome (PCOS) is a common endocrine disorder affecting 5–10% of women of reproductive age. It is characterized by chronic anovulation leading to menstrual disorders, and increased infertility. The syndrome can also manifest as hirsutism and acne. Aim of the study The aim of the study was to compare, over a duration of 6 months, the effects of drospirenone (DRSP) versus chlormadinone acetate (CMA) containing oral contraceptives (OCs) on clinical, hormonal, and metabolic parameters in 120 PCOS women. Materials and methods 120 women with the diagnosis of PCOS according to the Rotterdam 2003 criteria were recruited to the study. All patients were divided to two treatment groups of OCs, containing: 3 mg DRSP/30 mcg EE (ethinylestradiol) (60 patients) and 2 mg CMA/30 mcg EE (60 patients). Clinical parameters such as hirsutismus and acne were evaluated. Metabolic parameters such as serum insulin, glucose concentration, homeostatic model assessment of insulin resistance, body mass index, systolic and diastolic blood pressures were also measured. Among hormonal parameters, serum estradiol, luteinizing hormone, follicle-stimulating hormone, prolactin, testosterone, dehydroepiandrosterone sulfate, thyroid-stimulating hormone, and free thyroxine were measured. Results The use of both DRSP- or CMA-containing OCs provided similar positive therapeutic effects with regard to clinical, metabolic, and hormonal parameters. Among clinical parameters, like hirsutismus, after 6 months of continuous OC treatment, a statistically significant improvement was observed in both groups: DRSP ( p < 0.0001) and CMA OC treatment ( p < 0.0001). In addition, significant improvement was showed according to acne lesions both after DRSP ( p < 0.0001) and CMA treatments ( p < 0.0001). Among glucose, insulin levels and HOMA-IR, there were statistically significant higher levels in both groups after DRSP ( p < 0.0001, p < 0.0001, p < 0.05) and CMA OC treatment ( p < 0.02, p < 0.0001, p < 0.0001). Hormonal parameters such as LH, FSH, prolactin, testosterone and DHEA-S were statistically significant lower in both groups after DRSP ( p < 0.0001, p < 0.0001, p < 0.01, p < 0,002, and p < 0.0001) and CMA OC treatment ( p < 0.0001, p < 0.0001, p < 0.04, p < 0.002, and p < 0.0001). Conclusions Further research, however, is needed not only to define optimal duration, and to clarify the effects of treatment on long-term metabolic outcomes, but also to explore different treatment options and possible combined therapies.