Summary Background & aims Epidemiological data suggest that moderate red wine consumption reduces cardiovascular mortality and the incidence of diabetes. However, whether these effects are due to ethanol or to non-alcoholic components of red wine still remains unknown. The aim of the present study was to compare the effects of moderate consumption of red wine, dealcoholized red wine, and gin on glucose metabolism and the lipid profile. Methods Sixty-seven men at high cardiovascular risk were randomized in a crossover trial. After a run-in period, all received each of red wine (30 g alcohol/d), the equivalent amount of dealcoholized red wine, and gin (30 g alcohol/d) for 4 week periods, in a randomized order. Fasting plasma glucose and insulin, homeostasis model assessment of insulin resistance (HOMA-IR), plasma lipoproteins, apolipoproteins and adipokines were determined at baseline and after each intervention. Results Fasting glucose remained constant throughout the study, while mean adjusted plasma insulin and HOMA-IR decreased after red wine and dealcoholized red wine. HDL cholesterol, Apolipoprotein A-I and A-II increased after red wine and gin. Lipoprotein(a) decreased after the red wine intervention. Conclusions These results support a beneficial effect of the non-alcoholic fraction of red wine (mainly polyphenols) on insulin resistance, conferring greater protective effects on cardiovascular disease to red wine than other alcoholic beverages. www.isrctn.org : ISRCTN88720134.