In men with rheumatoid arthritis (RA), the confounding effect of adverse cardiovascular risk profile on the independent association of RA disease activity score (DAS) and major adverse cardiovascular events (MACEs) continues to be debated. The aim was to analyze the association of RA DAS with MACEs in a prospective cohort of men with RA enrolled in the VARA Registry at the Dallas site from January 2003 to October 2006. All subjects met American College of Rheumatology criteria for RA. All events were obtained by reviewing patient clinical data. DAS was categorized as low, 0 to 3.2; moderate, 3.2 to 5.09; and high, > or =5.1. Of 282 men (mean age 66 +/- 11.1 years), 231 had valid DASs (150, low; 60, moderate; and 21, high DAS) and were followed up for 4.4 +/- 2 years. Ninety-two subjects (32.6%; 95% confidence interval 27 to 38) experienced an MACE, a composite end point of death (9 patients; 10%), acute coronary syndrome (38 patients; 42%), coronary revascularization (47 patients; 49%), new-onset heart failure (37 patients; 40%), and stroke (15 patients; 16%). DAS was a significant predictor of MACEs (hazard ratio 1.31, 95% confidence interval 1.1 to 1.6, p = 0.01) independent of traditional risk factors. Compared with patients with low or moderate DASs, patients with high DASs had a lower mean event-free period (35 and 30 vs 19 years, respectively; p = 0.03). In conclusion, in a population of male US veterans aged >50 years, (1) patients with RA were at high risk of MACEs, and (2) RA DAS was a significant predictor of MACEs independent of traditional cardiovascular risk factors.