Coronary artery calcification (CAC) is associated with atherosclerotic complications. However, elevated CAC may not always imply a worse prognosis. Herein, we report the clinical evolution of long-term red wine (RW) drinkers in relation to CAC. We followed 200 healthy male habitual RW drinkers and compared them to 154 abstainers for a period of 5.5 years. The initial evaluation included coronary computed tomography angiography (CTA), clinical, demographics, and laboratory data. CAC was quantified by the Agatston score. The follow-up process was conducted by telephone calls and/or hospital record review. The composite end-point of total death, acute myocardial infarction (AMI), or coronary revascularization (or major adverse cardiac event - MACE) was assessed. The RW drinkers ingested 28.9±15 g of alcohol/day for 23.4±12.3 years. They had higher high-density lipoprotein and low-density lipoprotein, but lower C-reactive protein than abstainers. Age, total cholesterol, triglycerides, glucose, and liver enzymes were similar. History of diabetes was lower among drinkers, but other risk factors were similar. However, drinkers had higher CAC than abstainers; the mean value was 131.5±362 in drinkers vs 40.5±320 in abstainers (P<0.001). The median and interquartile range were 15 (0.0-131.5) in RW drinkers and 1 (0.0-40.5) in abstainers (P=0.003). During the follow-up, MACE was significantly lower in drinkers than in abstainers, despite their higher CAC. The difference was driven mainly by AMI (0 vs 6; P<0.03). Greater CAC values in this setting did not predict worse prognosis. A possible underlying mechanism is lesion calcification, which leads to plaque stabilization and less clinical events.