BACKGROUND: Symptoms of Multiple Sclerosis (MS) are related to a progressive and strong impact on patient’s quality of life (QoL). PRIMUS questionnaire is a MS-specific-instrument to assess QoL. OBJECTIVES: To assess QoL in MS patients using the PRIMUS questionnaire and the relationships between QoL, disease duration and EDSS disability. MATERIAL AND METHODS: Non-interventional, cross-sectional and multicenter study. 261 patients, >17 years with relapsing-remitting or secondary-progressive MS (RRMS/SPMS), treated with interferon beta-1b (≥6 months). PRIMUS questionnaire has three subscales: symptoms, activity limitations and QoL. For the present study, self-assessed changes were evaluated for QoL (0-22 score) and activity limitation (0-38 score) subscales. The higher scores the better QoL and the greater activity limitation. Correlations between PRIMUS-QoL and EUROQoL-5D, and with visual analog scale (VAS) were evaluated using Spearman-coefficient (S). RESULTS: Mean (SD) age was 41.7(10.3) years (61.3% women), 83.9% were RRMS diagnosed. Mean time since diagnosis was 7.6±5.8 years, higher in SPMS (6.9 ±5.2 vs. 11.2±7.4, p<0.0001). Mean EDSS disability was 2.6±1.75 (5.1±1.3 SPMS vs. 2.1±1.4 RRMS, p<0.0001). PRIMUS-QoL was better in RRMS patients: 18.3±6.8 vs. 9.9±7.1 (p<0.0001), getting worse as time from diagnosis increased (p<0.01) and with patient’s disability (18.8±6.6 in early stages [EDSS<3.5] and 8.4±6.3 in advanced ones [EDSS>5], p<0.0001). PRIMUS-activity showed a relationship between loss of activity with disease duration (p<0.0001) and patient’s disability (p<0.0001). PRIMUS-QoL showed a strong negative correlation (S=-0.7869) with EUROQoL-5D (as higher EUROQoL scores indicate worse QoL) and positive correlation with theVAS (S= 0.7272). PRIMUS-activity showed a very strong correlation (S=0.8179) with EUROQoL-5D as well as a strong negative correlation (S=-0.7571) with the VAS. CONCLUSIONS: The QoL of MS patients changes according to the disease types and disability levels, and it progressively worsens with disease duration. PRIMUS questionnaire has demonstrated to be a good tool for assessing QoL and activity in MS patients.