Objective: To determine the prevalence of insulin resistance (IR) in a large population of patients with the polycystic ovary syndrome (PCOS). Design: Prospective, case-control. Setting: University medical center. Patient(s): Two hundred seventy-one PCOS patients and 260 eumenorrheic, non-hirsute, control women. Intervention(s): History and physical examination and blood sampling. Main Outcome Measure(s): Total T, free T, DHEAS, sex hormone-binding globulin, and fasting glucose and insulin levels; homeostatic model assessment values for IR (HOMA-IR) and percent β-cell function (HOMA-%β-cell). Result(s): Patients with PCOS and controls differed significantly in all parameters studied, except fasting glucose. Because the HOMA-IR and HOMA-%β-cell values were variably associated with race, age, and body mass index, the HOMA-IR and HOMA-%β-cell values were then adjusted for these cofounders. After adjustment, 64.4% of PCOS patients were noted to be insulin resistant, and 2.6% had β-cell dysfunction. Compared with PCOS patients without IR (n = 96), patients with IR (n = 174) were more obese and had higher β-cell function. Conclusion(s): In patients with PCOS, the prevalence of IR was 64% according to the HOMA-IR measurement, after adjustment. Patients with IR were more clinically affected. Although IR is a common abnormality in PCOS, it does not seem to be a universal feature. ©2005 by American Society for Reproductive Medicine.