OBJECTIVES: Major depressive disorder (MDD) is associated with impaired patient functioning and significant reductions in health-related quality of life (HRQL). Antidepressant treatments aim to increase patient rates of sustained remission as early as possible, and our objective was to study the impact of early sustained remission on patient's HRQL. METHODS: A total of 250 patients with a DSM-IV diagnosis of MDD under treatment with selective serotonin reuptake inhibitors were selected for an observational 8-week follow-up study. Patient assessments included the Montgomery-Asberg Depression Rating Scale (MADRS), the Short Form-36 Item scale (SF-36) and the EuroQoL (EQ-5D). The MADRS was performed at baseline, weeks 2, 3, 4 and 8 and HRQL scales were performed at baseline and week 8. Remission was defined using the MADRS cut-off value of 12. Five subgroups were defined: remitters at week 2 (G1), week 3 (G2), week 4 (G3), week 8 (G4) and non-remitters at week 8 (G5). Multivariate analyses of variance were used to assess the differences of HRQL among these groups after adjustment on centre and baseline MADRS scores. RESULTS: The distribution of patients across groups was 6.7% (G1), 16.8% (G2), 12.4% (G3), 21.2% (G4) and 42.9% (G5). After adjustment, HRQL assessed by EQ-5D was significantly higher for remitters (G1: 0.81±0.08; G2: 0.79±0.16; G3: 0.77±0.20; G4: 0.71±0.21; G5: 0.57±0.28; p<0.001). The same results were found with the SF-36 Physical and Mental Composite Summary scores (p <0.001 for both) as well as SF-36 subscales (p <0.001). Early sustained remitters reported higher EQ-5D scores (G1 and G2 versus G3 and G4, p <0.05). CONCLUSION: The results of this observational study clearly show the major impact of sustained remission on HRQL in MDD. Time to sustained remission may have a major impact on patient's HRQL and might become a pre-requisite for approval and reimbursement of new antidepressant compounds.