Objective: Fatty acids (FA) influence lipoprotein levels and take part in metabolic pathways of inflammation and thrombosis, potentially representing a risk marker or an emerging cardiovascular risk factor. The purpose of this study was to search for independent predictors of blood fatty acid distribution in subjects with and without coronary heart disease (CHD). Methods: In this case-control study, 179 patients with CHD and 155 healthy age- and gender- frequency matched subjects were included. Clinical variables (anthropometric data, traditional risk factors, current drug therapies) and life habits (diet by EPIC food frequency questionnaire, smoke, physical activity) were compared, between CHD patients and controls in univariate analysis. Clinical features that differed significantly were included in a multivariate linear regression analysis to assess their independent association with levels of blood fatty acid types and classes (assessed by gas chromatography). Results: a) Fish intake was associated positively with n-3 and negatively with n-6 FA; b) coronary disease was associated positively with total saturated FA, C16:0 and C24:0, and negatively with C16:1n-7, C20:3n-6, C20:3n-9, and estimated ?9 stearoyl-CoA desaturase (16:1n7/16:0 ratio); c) statins use was associated negatively with C18:2n-6 and C18:3n-3, and positively with C18:3n-6, C20:4n-6, the estimated ?6 desaturase (C18 :3n-6/C18 :2n-6 ratio), C20:4n-6/C18:2n-6, C20:5n-3/C18:3n-3 and C22:6n-3/C18:3n-3 ratios. Conclusions: The blood fatty acid distribution is associated, besides with diet quality, with the CHD status and with statin utilization, possibly in relation to a distinct fatty acid metabolism in patients prone to CHD and to pleiotropic effects of statins beyond LDL-C lowering.