Polycystic ovary syndrome (PCOS) is a common endocrine condition associated with long-term cardiovascular risk factors. PCOS women often present with obesity, metabolic abnormalities (insulin resistance and dyslipidemia) and preliminary data has suggested autonomic imbalance [elevated sympathetic nervous system (SNS) activity and decreased heart rate variability (HRV)] as well as endothelial dysfunction. However it is not clear whether these abnormalities are driven by the underlying level of obesity and metabolic disturbance or whether they are independently related to PCOS. We therefore examined multi unit and single unit muscle SNS activity (by microneurography), HRV (time and frequency domain analysis or short term R-R intervals) and endothelial function [ischemic reactive hyperaemia index (RHI) using the EndoPat device] in 20 overweight women with PCOS (BMI: 31±1 kg/m2, age: 32±2 years) and compared them to 23 control overweight women (BMI: 33±1 kg/m2, age: 29±2 years) presenting the same metabolic profile (total, HDL and LDL cholesterol, fasting glucose, triglycerides and blood pressure). PCOS women had elevated multiunit muscle SNS activity (40±2 vs 33±3 bursts per 100 heartbeats, P<0.05). Single unit analysis showed that vasoconstrictor neurons were characterized by elevated firing rate and probability and incidence of multiple spikes in PCOS compared with control women (P<0.01 for all parameters). PCOS women also had impaired endothelial function (RHI: 1.77±0.03 vs 2.16±0.14, P<0.05). HRV did not differ between the 2 groups. PCOS women have increased sympathetic drive and impaired endothelial function greater than that expected from obesity and metabolic disturbances alone. Sympathetic activation and endothelial dysfunction may confer greater cardiovascular risk in women with PCOS.