Analysis of 30,580 Spanish adults across two major cohorts reveals that moderate wine consumption within Mediterranean diet patterns reduces all-cause mortality by 33% compared to wine-free adherence. In the high-risk PREDIMED trial, participants following Mediterranean diet with moderate wine (up to 7 glasses weekly) showed a 45% lower cardiovascular disease risk versus wine-free adherence, while mortality dropped from 23% to 33% reduction when wine was included. This represents one of the largest longitudinal investigations into wine's specific contribution to Mediterranean diet benefits, with follow-up extending to 22 years in some participants. The dose-response relationship proves critical—protective effects disappeared at three or more daily glasses, reinforcing moderation's importance. However, the authors' caution about abstainer bias and non-significant interaction terms highlights methodological challenges in alcohol research. These findings support the emerging consensus that alcohol's health effects depend heavily on dietary context and consumption patterns. For adults following Mediterranean-style eating, moderate wine consumption appears synergistic with other protective components like olive oil and vegetables, potentially through enhanced antioxidant absorption and anti-inflammatory mechanisms that operate differently than isolated alcohol consumption.