We evaluated prospectively the predictive value of serum apolipoprotein (apo) A-II, the second major apolipoprotein of high-density lipoprotein (HDL), for cardiometabolic risk in Turkish adults showing abnormalities in other proteins that normally confer protection.Determinants of apoA-II and its associations with coronary heart disease (CHD), metabolic syndrome (MetS) and diabetes were investigated at 4 years follow-up in 193 elderly men and women.ApoA-II concentrations at baseline, in addition to being significantly related to HDL-cholesterol, were directly associated with complement C3 in multivariate linear regression analyses comprising nine variables. Following adjustment for gender, age and HDL-cholesterol (>30/>33 g/L, in men and women, respectively), low serum apoA-II concentrations predicted incident MetS [relative risk (RR) 3.5 (95% CI 1.4; 8.6)] and type 2 diabetes [RR 4.5 (95% CI 1.3; 15.6)] in both genders at an increment of 1 SD. Increased apoA-II values were not associated with prevalent or incident CHD, and tended to be marginally atheroprotective only in males.Serum apoA-II concentrations confer risk for MetS and diabetes and exhibit evidence of anti-inflammatory properties among Turks. These findings support the effects seen for several other HDL protein constituents. This finding may explain the increased cardiometabolic risk among Turks.