BACKGROUND AND AIM: We sought to investigate the relationship between fish consumption and the risk of developing non-fatal acute coronary syndromes (ACS) among current smokers. METHODS AND RESULTS: During 2000-2001, we conducted the CARDIO2000 case-control study that included patients hospitalized for a first event of ACS and matched (age, sex) individuals without clinical evidence of CHD (controls), from all the Greek regions. In the present analysis we studied data from 519 men (59+/-10 years old) and 45 women (62+/-9 years old) patients, as well as 444 men and 90 women controls, matched for age with the patients that reported current smoking. To evaluate the hypothesis tested we applied conditional logistic regression analysis after controlling for several potential confounders. Overall, 94% of controls and patients reported fish consumption at least once a week. Compared to low fish consumption (<60 g/week), moderate (60-180 g/week) intake was associated with 15% (p<0.05) lower risk of ACS, while increased (180-300 g/week, or >300 g/week) consumption was associated with 18% (p<0.05) and 19% (p = 0.53) higher risk, respectively. CONCLUSION: Moderate fish consumption seems to moderate the deleterious effect of smoking on the occurrence of ACS. However, increased intake does not seem to confer any benefit on coronary risk.