RATIONALE: Although a number of studies investigated the link between major depressive disorder (MDD) and metabolic syndrome (MetS), the association between MetS and treatment-resistant depression (TRD) is still not clear. ----- OBJECTIVES: The aim of the study was to investigate the relationship between TRD and MetS and/or components of MetS and cardiovascular risk factors. Given the high prevalence of both conditions, the hypothesis was that TRD would be significantly associated with MetS. ----- METHODS: This cross-sectional study included 203 inpatients with MDD, assessed for the treatment resistance, MetS and its components, and severity of MDD. Diagnoses and evaluations were made with SCID based on DSM-IV, National Cholesterol Education Program Adult Treatment Panel III criteria, and the Hamilton Depression Rating Scale. ----- RESULTS: TRD prior to study entry was found in 26.1 % of patients, while MetS was observed in 33.5 % of patients. The prevalence of MetS did not differ significantly between TRD and non-TRD patients. In addition, the frequency of the altered values of particular components of the MetS or cardiovascular risk factors was not associated with treatment resistance in depressed patients. Patients with TRD were older, had a higher number of lifetime episodes of depression and suicide attempts, and longer duration of MDD compared to non-TRD patients. ----- CONCLUSIONS: The occurrence of either MetS or the particular components of the MetS and other cardiovascular risk factors was similar between TRD and non-TRD patients. Although there is a bidirectional relationship between depression and MetS, neither MetS nor its components appear to influence treatment resistance to antidepressants.