Overweight women with polycystic ovary syndrome (PCOS) were randomized to a high protein (HP; 40% carbohydrate and 30% protein; n = 14) or a low protein (LP; 55% carbohydrate and 15% protein) diet (n = 14). The intervention consisted of 12 wk of energy restriction (approximately 6000 kJ/d), followed by 4 wk of weight maintenance. Pregnancies (two HP and one LP); improvements in menstrual cyclicity, lipid profile, and insulin resistance (as measured by the homeostasis model); and decreases in weight (7.5%) and abdominal fat (12.5%) occurred independently of diet composition. Improvements in menstrual cyclicity were associated with greater decreases in insulin resistance and fasting insulin (P = 0.011). On the LP diet, high density lipoprotein cholesterol decreased 10% during energy restriction (P = 0.008), and the free androgen index increased 44% in weight maintenance stages (P = 0.027). Weight loss leads to improvements in cardiovascular and reproductive parameters potentially mediated by improvements in surrogate measures of insulin resistance. An HP weight loss diet may result in minor differential endocrine and metabolic improvements.