The Pioglitazone in the Prevention of Diabetes (PIPOD) study was a single arm 3-year open-label pioglitazone treatment to determine the effects of pioglitazone in women with prior gestational diabetes mellitus (GDM) who had completed the troglitazone in the Prevention of Diabetes (TRIPOD) study. Here we report the results on progression of subclinical atherosclerosis, measured by carotid intima-media thickness (CIMT) in non-diabetic women. Data were analyzed to compare CIMT progression rates during pioglitazone treatment to rates that had been observed during either placebo or troglitazone treatment in the TRIPOD study. Sixty-one women met the entry criteria with mean age of 40 years. In the 30 women who came to PIPOD from the placebo arm of TRIPOD, the CIMT rate was 69% lower during pioglitazone treatment than it had been during placebo (0.0031 vs. 0.0100mm/yr, p=0.006). In the 31 women who came to PIPOD from the troglitazone arm of TRIPOD, CIMT rate was 38% lower during pioglitazone than it had been during troglitazone, a difference that was not statistically significant (0.0037 vs. 0.0060mm/year; p=0.26). Adjustment for differences in baseline characteristics and potential on-trial confounders did not alter the conclusion but did increase the CIMT rates differences slightly. We conclude that treatment with pioglitazone slowed CIMT progression in women who had been on placebo in the TRIPOD study and maintained a relatively low rate of progression in women who had been on troglitazone. Pioglitazone slows progression of subclinical atherosclerosis in young Hispanic women at increased risk for type 2 diabetes.