INTRODUCTION: Health related quality of life (HRQOL) is often affected in multiple sclerosis (MS). Nevertheless, to our knowledge, there is no longitudinal study in the literature about the correlation between MRI parameters and HRQOL in MS patients. METHODS: We included 28 patients with clinically definite relapsing remitting MS. All patients initiated subcutaneous interferon beta-1a therapy. To assess HRQOL, we used the SEP-59 scale, the French validated translation of MSQOL-54, and the MusiQoL scale. Conventional MRI was performed every year. Lesion load (LL) and brain atrophy were automatically measured using SepINRIA, a free software developed by INRIA in Sophia Antipolis. RESULTS: The mean EDSS score was 1.7 and disease duration was 2.5 years. Our results revealed that HRQOL was significantly correlated to T1 and T2-LL with both SEP-59 and MusiQoL scales. T1-LL was better correlated with physical dimensions and T2-LL was better correlated with mental components. At 1-year follow-up, patients whose MRI showed either an increase of T1 LL or at least one gadolinium enhancing lesion had a worse HRQOL at the end of the study. Initial brain parenchymal fraction (BPF) measure was also correlated with the long-term follow-up HRQOL. EDSS scored at the end of the study had not significantly changed (1.3; P>0.05). CONCLUSION: Our study revealed pertinent clinicoradiological correlations between HRQOL and MRI parameters in our cohort.