A reduction of plasma fibrinogen has been suggested as one mechanism through which physical activity would protect against coronary heart disease (CHD). Therefore, we investigated the association of conditioning leisure time physical activity (CLTPA), assessed quantitatively by a 12-month history, and maximal oxygen uptake (VO2max) with plasma fibrinogen concentration in eastern Finnish men aged 42-60 years. A high mean intensity of CLTPA (standardized multivariate regression coefficient beta -0.059, p = 0.020) and a high maximal oxygen uptake (beta -0.163, p < 0.001) were associated with reduced plasma fibrinogen when adjusting for the strongest covariates. The adjusted relative difference in plasma fibrinogen concentration was 6.6% between men with a mean CLTPA intensity of < 4 and > 8 METs and 9.1% between the extreme quartiles of VO2max (< 2.21 vs > 2.961/min). The association between the mean intensity of CLTPA (p = 0.030 for interaction) and VO2max (p = 0.033) and plasma fibrinogen was stronger for smokers than for non-smokers. These data indicate that a reduction of plasma fibrinogen concentration may be one mechanism through which moderate to high intensity CLTPA and high cardiorespiratory fitness reduce the risk of CHD.