INTRODUCTION: Obesity is associated with decreased heart rate variability (HRV). Rosiglitazone, a PPARgamma agonist, is generally associated with increases in body mass. PURPOSE: To assess whether the gain in body mass and adiposity expected from rosiglitazone treatment has an influence on HRV in patients with type 2 diabetes and coronary artery disease. METHODS: One hundred and twenty-five patients with type 2 diabetes and coronary artery disease aged between 40 and 75 years were studied. Anthropometric measurements: (1) body mass index (BMI), (2) waist circumference (WC), (3) abdominal computed tomography (CT) scan, and HRV (using a 24 h Holter) were measured at baseline and after 12 months of treatment. Patients were randomized to rosiglitazone or placebo regimen. RESULTS: In the rosiglitazone vs. placebo group, there were significant increases in body mass [3.5 (2.6;4.4); mean (95 % CI) vs. 0.2 (-0.4;0.8)] kg), BMI [1.3 (1.0;1.6) vs. 0.1 (-0.1;0.3) kg/m(2)], WC [2.1 (0.9;3.3) vs. 0.4 (-0.4;1.2) cm, all p </= 0.001] and subcutaneous adipose tissue [253 (187;319) vs. 6 (-24;36) cm(3), p </= 0.001] without statistically significant changes in visceral adipose tissue [-22 (-91;47) vs. 57 (43;71) cm(3), p = 0.546], respectively. There was no change in HRV in either group after 12 months. There were no correlations between changes in HRV variables and fat distribution. CONCLUSION: Our results suggest that changes in adiposity indices observed after 12 months of rosiglitazone therapy have no deleterious influence on HRV in patients with type 2 diabetes and coronary artery disease.