There is strong evidence from meta-analyses of prospective epidemiological studies that increasing plasma fibrinogen levels are associated with an increasing risk of cardiovascular disease (CVD) and all-cause mortality. However, there are few published direct comparisons of the several different available fibrinogen assays in association with CVD or mortality. We therefore prospectively compared the standardized von Clauss assay of clottable fibrinogen with three other assays: prothrombin time (PT)-derived clottable fibrinogen, immunonephelometric fibrinogen, and heat precipitable fibrinogen in the Scottish Heart Health Extended Cohort. Hazard ratios (HRs) for a standard deviation increase in fibrinogen for risk of CVD, adjusted for age and sex, were 1·17 (95% confidence interval [CI] 1·14; 1·21) for the von Clauss assay; 1·19 (1·06; 1·33) for the heat precipitation assay; 1·16 (1·01; 1·35) for the PT-derived assay; and 1·28 (1·10; 1·51) for the immunonephelometric assay. HRs for all-cause mortality were 1·21 (1·18; 1·24); 1·13 (1·01; 1·26), 1·17 (1·00; 1·37) and 1·17 (0·99; 1·39), respectively. No significant differences were observed between the assays in such comparisons. We therefore conclude that the choice between plasma fibrinogen assays in routine clinical haematology and biochemistry laboratories should depend on practical factors, and not on expected differences in the strength of associations.