Aims/hypothesis We previously reported that the plasma levels of the endocannabinoid, 2-arachidonoylglycerol (2-AG), in a cohort of viscerally obese men are directly correlated with visceral adipose tissue (VAT) accumulation and metabolic risk factors including low HDL-cholesterol and high triacylglycerol. It is not known, however, if such correlations persist after vigorous lifestyle interventions that reduce metabolic risk factors. We analysed the changes in endocannabinoid levels in a subsample from the same cohort following a 1 year lifestyle modification programme, and correlated them with changes in VAT and metabolic risk factors. Methods Forty-nine viscerally obese men (average age 49 years, BMI 30.9 kg/m 2 , waist 107.3 cm) underwent a 1 year lifestyle modification programme including healthy eating and physical activity. Plasma levels of 2-AG and the other most studied endocannabinoid, anandamide, were measured by liquid chromatography-mass spectrometry. Anthropometric and metabolic risk factors, including VAT, insulin resistance and glucose intolerance, HDL-cholesterol and triacylglycerol, were measured. Results Most risk factors were improved by the intervention, which led to a significant decrease in body weight (−6.4 kg, p<0.0001), waist circumference (−8.0 cm, p<0.0001) and VAT (−30%, p<0.0001), and in plasma 2-AG (−62.3%, p<0.0001) and anandamide (−7.1%, p=0.005) levels. The decrease in levels of 2-AG but not those of anandamide correlated with decreases in VAT and triacylglycerol levels, and with the increase in HDL 3 -cholesterol levels. Multivariate analyses suggested that decreases in 2-AG and VAT were both independently associated with decreases in triacylglycerol.Conclusions/interpretation This study shows that a strong correlation exists between 2-AG levels and high plasma triacylglycerol and low HDL 3 -cholesterol in viscerally obese men.