Atherosclerosis is considered a low-grade inflammatory disease. Polyphenol-rich alcoholic beverages (red wine) have shown a more pronounced antiinflammatory effect than polyphenol-free alcoholic beverages (gin). However, no studies to our knowledge have evaluated the antiinflammatory effects of alcoholic beverages with medium-level polyphenol content such as cava (sparkling wine). We enrolled 20 healthy men (aged 34 6 9 y) in a randomized crossover study to receive 30 g ethanol/d as cava or gin for 28 d. Before both interventions, subjects abstained from alcohol for 2 wk. Inflammatory biomarkers of atherosclerosis and expression of adhesion molecules on peripheral leukocytes were measured before and after each intervention. Likewise, dietary intake and exercise were also evaluated. Expression of lymphocyte function associated antigen-1 (LFA-1), very late activation antigen-4 (VLA-4), Sialyl-Lewisx (SLex), and CD40 on monocytes decreased after cava intake (all P , 0.05), whereas only SLex was reduced after gin intake (P ¼ 0.036). Circulating markers of atherosclerosis including vascular cell adhesion molecule-1, E-selectin, and P-selectin decreased after both interventions (all P , 0.05). High-sensitivity C-reactive protein, intercellular adhesion molecule-1 (ICAM-1), IL-6, monocyte hemoattractant protein-1 (MCP-1), and CD40L were diminished only after cava intake (all P , 0.05). The effects of cava on circulating CD40L, ICAM-1, and MCP-1, and monocyte surface expression of CD40, LFA-1, and VLA-4 were greater than those of gin (all P , 0.05). In conclusion, both cava and gin showed antiinflammatory properties; however, cava had a greater protective effect, probably due its polyphenol content.