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Obese individuals, despite having increased cardiovascular (CV) risk factors experience adverse CV outcomes less frequently than non-obese. Little is known about association of long-term weight gain to development of coronary artery disease (CAD), inflammation and thrombogenicity. 418 consecutive patients with suspected CAD undergoing elective cardiac catheterization were included in a sub-analysis of the multi analyte, thrombogenic, and genetic markers of atherosclerosis study. Maximum weight gain (MWG) was defined as percentage increase in weight since age 17 years to year of heaviest weight and categorized as: minor (<30 %), moderate (30-47 %), severe (>47-69 %), and extreme (>69 %). Lipid profiling was determined by vertical density gradient ultracentrifugation, thrombin-induced platelet fibrin clot strength (TIP-FCS) by thrombelastography, and urinary 11-dehydrothromboxane B2 (11-dhTxB2) by ELISA. CAD severity was defined as minimal (<20 %), moderate (20-75 %), and severe (>75 %) luminal diameter obstruction of any major coronary vessel. The mean MWG was 53 ± 33 %. Extreme MWG group had a higher incidence of diabetes mellitus (48 %), hypertension (81 %), depression (25 %), and were most often female (60 %) (p < 0.05 for all). In women, CAD severity was inversely associated to MWG (p = 0.05), whereas in men no such association was observed (p = 0.18). TIP-FCS increased in a stepwise fashion with MWG (p = 0.001). 11-dTxB2 levels were higher in the extreme MWG group, regardless of lipid lowering therapy (p < 0.05). Our data suggest that maximal weight gain since age 17 years is associated with heightened thrombogenicity, inflammation and a poorer lipid profile but not an increased risk for severe CAD development.