Inflammation can predispose to myocardial infarction (MI), and mannan binding lectin (MBL) promotes phagocytic clearance of inflammatory agents, but the predictive value of MBL levels for MI is not known. MBL was analyzed in subgroups of the population-based Reykjavik study, a cohort of 19,381 participants recruited from 1967. MBL levels were very stable over time (self correlation: 0.86). In a cross-sectional group from the original cohort (n = 987), high MBL (>1,000 microg/L) was associated with a greatly lowered odds ratio for MI (0.64, P < 0.001). To verify this finding, a nested case control sample (n = 1,309) was randomly selected from the cohort. High MBL at recruitment was also associated with decreased MI risk in this follow-up group, but to a lesser extent and not significant for the whole group, smokers, or hypertensive individuals. However, high MBL was as in the cross-sectional group, associated with greatly decreased MI risk in diabetic (P = 0.02) or hypercholesterolemic individuals (P = 0.004). This also applied to raised erythrocyte sedimentation rate (P = 0.007). Diabetic patients with high MBL did not have a higher MI risk than nondiabetic individuals. Our findings indicate that high MBL may predict decreased likelihood of MI, particularly in diabetics, and are consistent with the possibility that MBL may promote clearance of atherogenic agents.