OBJECTIVES: Multiple sclerosis (MS) is a chronic neurological disease characterized by sudden isolated attacks (relapses) often resulting in disability. This study evaluates the effect that increasing disability has on quality of life in Relapsing Remitting MS (RRMS) patients in Brazil and Mexico. METHODS: Physician and patient-reported data were identified from the 2015 Adelphi MS Disease Specific Programme, a cross-sectional study of MS patients in Brazil and Mexico. Multiple linear regression analyses modelled the relationship between the Expanded Disability Status Scale (EDSS, a measure of disease disability) and EQ-5D (a standardized instrument used as a measure of health outcome) and Hamburg Quality of Life Questionnaire in Multiple Sclerosis (HAQUAMS, an MS-specific instrument used to determine quality of life).  RESULTS: Neurologist-completed records provided full demographics and details of disease management for 112 RRMS patients in Brazil (n=80 EDSS<3; n=15 EDSS 3-5; n=17 EDSS>5) and 95 RRMS patients in Mexico (n=55 EDSS<3; n=25 EDSS 3-5; n=15 EDSS>5) in the analysis. Brazilian patients with increased disability had a worse quality of life according to EQ-5D (-0.11, p=0.107, EDSS 3-5; -0.38, p=0.006, EDSS>5), EQ-VAS (-12.68, p=0.002, EDSS 3-5; -31.62, p=0.006, EDSS>5), and HAQUAMS overall score (+0.54, p=0.038, EDSS 3-5; +0.76, p=0.114, EDSS>5). Mexican patients with increased disability had worse quality of life according to EQ-5D (-0.20, p=0.010, EDSS 3-5; -0.18, p=0.011, EDSS>5) EQ-VAS (-10.94, p=0.04, EDSS 3-5; -36.19, p=0.000, EDSS>5), and HAQUAMS Mobility/Lower Limb subscale (+0.70, p=0.039, EDSS 3-5; +1.14, p=0.022, EDSS>5), HAQUAMS Social function subscale (+0.39, p=0.022, EDSS 3-5; +0.66, p=0.008, EDSS>5), HAQUAMS Mood subscale (+0.50, p=0.060, EDSS 3-5; +0.73, p=0.015, EDSS>5). CONCLUSIONS: RRMS patients with increased disability, as measured by EDSS, in Brazil and Mexico experience worse quality of life demonstrated by differences in EQ-5D and HAQUAMS. Interventions that can slow or delay the progression of disability may therefore positively impact patients’ quality of life.