Background— Once- or twice-weekly consumption of fish (or a small amount of fish intake) reduces the risk of coronary heart disease and sudden cardiac death in Western countries. It is uncertain whether a high frequency or large amount of fish intake, as is the case in Japan, further reduces the risk. Methods and Results— To examine an association between high intake of fish and n3 polyunsaturated fatty acids and the risk of coronary heart disease, a total of 41 578 Japanese men and women aged 40 to 59 years who were free of prior diagnosis of cardiovascular disease and cancer and who completed a food frequency questionnaire were followed up from 1990–1992 to 2001. After 477 325 person-years of follow-up, 258 incident cases of coronary heart disease (198 definite and 23 probable myocardial infarctions and 37 sudden cardiac deaths) were documented, comprising 196 nonfatal and 62 fatal coronary events. The multivariable hazard ratios (HRs) and 95% confidence intervals in the highest (8 times per week, or median intake=180 g/d) versus lowest (once a week, or median intake=23 g/d) quintiles of fish intake were 0.63 (0.38 to 1.04) for total coronary heart disease, 0.44 (0.24 to 0.81) for definite myocardial infarction, and 1.14 (0.36 to 3.63) for sudden cardiac death. The reduced risk was primarily observed for nonfatal coronary events (HR=0.43 [0.23 to 0.81]) but not for fatal coronary events (HR=1.08 [0.42 to 2.76]). Strong inverse associations existed between dietary intake of n3 fatty acids and risk of definite myocardial infarction (HR=0.35 [0.18 to 0.66]) and nonfatal coronary events (HR=0.33 [0.17 to 0.63]). Conclusions— Compared with a modest fish intake of once a week or &20 g/d, a higher intake was associated with substantially reduced risk of coronary heart disease, primarily nonfatal cardiac events, among middle-aged persons.