Few and mostly uncontrolled studies indicate that weight loss improves heart rate variability (HRV) in grade-3 obesity. The aim of this study was to compare in grade-3 obesity surgery and hypocaloric diet on clinical and metabolic variables and on autonomic indices of HRV. Twenty-four subjects (body mass index, BMI 45.5 +/- 9.13 kg/m(2)) underwent surgery (n = 12, gastric banding, LAGB) or received hypocaloric diet (n = 12, 1,000-1,200 kg/day). Clinical [BMI, systolic blood pressure (SBP) and diastolic blood pressure (DBP), heart rate] and metabolic variables [glucose, cholesterol, HDL- and LDL-cholesterol, triglycerides, AST and ALT transaminases] and 24-h Holter electrocardiographic-derived HRV parameters [R-R interval, standard deviation of R-R intervals (SDNN); low/high-frequency (LF/HF) ratio, and QT interval] were measured at baseline and after 6 months. The two groups were identical at baseline. BMI (-7.5 +/- 3.57 kg/m(2), mean +/- SD), glucose (-24.1 +/- 26.77 mg/dL), SBP (-16.7 +/- 22.19 mmHg) and DBP (-6.2 +/- 8.56 mmHg) decreased in LAGB subjects (p < 0.05) and remained unchanged in controls. At 6 months, SDNN increased in LAGB subjects (+25.0 +/- 37.19 ms, p < 0.05) and LF/HF ratio diminished (2.9 +/- 1.84 vs. 4.9 +/- 2.78; p = 0.01), with no change in controls; LF (daytime) and HF (24 h and daytime) increased in LAGB subjects, with no change in controls. Decrease in BMI correlated with SBP and DBP decrease (p < 0.05), and DBP decrease correlated with HR decrease (p < 0.05) and QT shortening (p < 0.05). Weight loss is associated with improvement of glucose metabolism, of blood pressure, and with changes in time and frequency domain parameters of HRV; all these changes indicate recovery of a more physiological autonomic control, with increase in parasympathetic and reduction in sympathetic indices of HRV.