Background Long-term smoking is believed to cause endothelial dysfunction via increased oxidative stress, whereas short-term smoking impairs vasodilatation through an as yet undefined mechanism. However, red wine and its constituents have a powerful antioxidant effect both in long-term and acute consumption: The aim of the current study was to investigate whether red wine, with or without alcohol, influences endothelial dysfunction induced by acute cigarette smoking. Methods Sixteen healthy volunteers (8 males and 8 females) were recruited for a double-blind, crossover study, comprising 3 study days. Each subject smoked 1 cigarette, or smoked and drank 250 mL of red wine, or smoked and drank 250 mL of dealcoholized red wine. Flow-mediated dilatation (FMD) was measured after fasting and 1.5, 30, 60, and 90 minutes after each trial (smoke or smoke and drink either beverage). Results Acute smoking of 1 cigarette caused a reduction in FMD (P < .001), which was statistically significant 15, 30, and 60 minutes after the inhalation of smoke compared to baseline levels (P < .001, P < .001, P = .043, respectively). However, simultaneous ingestion of either red wine or dealcoholized red wine with smoking did not lead to, a change in FMD. Conclusions Acute smoking caused a significant impairment in endothelial function. Simultaneous consumption of red wine or dealcoholized red wine with smoking decreased smoke's harmful effect on endothelium.