Increased insulin resistance (IR) is a cardinal feature of overweight patients with polycystic ovarian syndrome (PCOS). However, there are no data on the variability of IR for subjects with PCOS. The biological variation of IR (homeostasis model assessment model) was assessed by measuring IR at 4-d intervals on 10 consecutive occasions in 12 overweight PCOS patients (median age, 28 yr; range, 18-31 yr) and 11 weight-matched control women having regular menses and without PCOS (median age, 30 yr; range, 19-33 yr). The distribution of IR was log Gaussian in PCOS and Gaussian distribution in the control group. The IR in PCOS subjects was significantly greater than in the controls [mean (range), 5.85 U (1-42.1) vs. 1.67 U (0.48-3.49); P = 0.001]. After accounting for analytical variation, the mean intraindividual variance was also substantially greater in PCOS patients than in controls (mean, 1.19 vs. 0.23). As a consequence, at any level of IR, a subsequent sample must rise by more than 322% or fall by more than 31% to be considered significantly different from the first. IR, measured using the homeostasis model assessment model, is significantly greater and more variable for overweight patients with PCOS. Therefore, this inherent variability needs to be accounted for in studies of IR in PCOS.