BACKGROUND: Resistant starch (RS) is a type of dietary fiber that can improve glucose metabolism, but its effects may be modulated by sex or baseline insulin sensitivity. This study was designed to examine the effect of high-amylose maize resistant starch (HAM-RS2) on insulin sensitivity (SI) in women, and to determine if SI status affects the response to RS. METHODS: This was a randomized, placebo-controlled, double-blind, cross-over study. Participants were 40 healthy, non-diabetic women aged 22-67 years in the normal-weight to obese BMI range (20.6-47.4 kg/m(2)). Two doses of HAM-RS2 were tested, 15 and 30 g per day, administered in the form of cookies. Participants were randomized to the order in which they received the experimental and placebo product. Each arm was 4 weeks, with a 4-week wash-out period in between. SI was assessed at the end of each 4-week arm of product consumption by frequently-sampled, insulin-modified, intravenous glucose tolerance test and minimal modeling. Participants were categorized as being insulin resistant (IR; SI < 7.8) or insulin sensitive (IS; SI ≥ 7.8) based on Gaussian analysis. The effect of treatment arm on SI was examined by mixed-model analysis within IR and IS sub-groups, using all available data. In addition, SI was examined by ANOVA among just those women who completed all three arms of the study with valid SI results. RESULTS: Among IR participants, SI was on average ~16 % higher after the 30 g arm when compared to the control arm by mixed-model analysis (n = 40, P < 0.05), and tended to be 23 % higher by ANOVA among women who completed all arms (n = 23, P = 0.06). HAM-RS2 did not affect SI in IS women. CONCLUSION: Consumption of HAM-RS2 at 30 g/day in the form of a snack food item was associated with improved insulin sensitivity in women with insulin resistance. CLINICAL TRIALS REGISTRY NUMBER: NCT0152806.