AIM To examine whether fasting blood lipid profiles are associated with the risk of myocardial infarction among Japanese men. METHODS We conducted a nested case-control study in the Morbidity of Myocardial Infarction Multicenter Study in Japan (3M Study). For each case of myocardial infarction entered in the 3M Study between 1997 and 2000, we randomly selected two controls, matched for age (+/-3 years), from among the participants in risk factor surveys with no history of myocardial infarction. A total of 723 male employees (241 cases and 482 controls) aged 35 to 65 years were enrolled in the present study. RESULTS The subjects had significantly higher mean fasting LDL-cholesterol and triglyceride, and lower mean HDL-cholesterol than controls. The multivariable conditional odds ratio (95% confidence interval) for myocardial infarction after adjustment for known cardiovascular risk factors was 3.87 (1.27-11.7, p for trend <0.001) for total cholesterol [-6.71 vs <4.65 mmol/L], 3.28 (1.12-9.60, p for trend=0.001) for LDL-cholesterol [-4.64 vs <2.59 mmol/L], 0.17 (0.07-0.43, p for trend=0.001) for HDL-cholesterol [-1.55 vs <1.03 mmol/L] and 3.03 (1.37-6.70, p for trend= 0.01) for triglycerides [-2.26 vs <1.13 mmol/L]. CONCLUSION High total and LDL-cholesterol, low HDL-cholesterol and high triglycerides levels were independently associated with an increased risk of myocardial infarction among middle-aged Japanese male workers.