OBJECTIVES: Multiple sclerosis (MS) and Alzheimer’s Disease (AD) are chronic and progressive diseases that have the potential to impose a significant burden on both caregivers and the immediate families of patients.  Extensive literature has documented MS and AD caregiver burden on physical and mental health; but there are no direct comparisons of MS and AD caregivers. This study examined the extent of MS caregiver burden compared to non-caregivers and caregivers of AD patients. METHODS: Data were obtained from the 2009 National Health and Wellness Survey administered online to a US representative adult sample (N=75,000).  Respondents reported health status, quality of life, work productivity, healthcare utilization and caregiver status. Multivariable regressions, adjusting for key characteristics (e.g., age, gender, marital status, depression), were conducted to explore differences between MS caregivers (n=215) vs. non-caregivers (n=69,224), as well as MS caregivers vs. AD caregivers (n=1,341).  Rate ratios (RR) and regression weights (b) are reported. RESULTS: Compared to non-caregivers , MS caregivers had significantly greater activity impairment (RR=1.41;p=0.01) and poorer mental (b=-1.44;p=0.015), physical (b=-1.96;p=0.002), and health utility scores (b=-0.03;p=0.002), along with more traditional healthcare provider visits (RR=1.46;p<0.0001), ER visits (RR=2.16;p<0.0001), and hospitalizations (RR=2.20;p=0.001) after covariate adjustment. Compared to AD caregivers, MS caregivers had greater activity impairment (RR=1.29;p=0.044) and more ER visits (RR=1.60;p=0.017) and hospitalizations (RR=1.92;p=0.008) after covariate adjustment.  Work productivity differences were not observed in comparison with either group, potentially due to the small number of employed MS caregivers in the sample (n=126). CONCLUSIONS: MS caregivers had significantly more burden compared with non-caregivers.  In addition, the results suggest an even greater burden to these individuals than observed among AD caregivers.  The results of this analysis of a national survey reveal the hidden toll of those providing care for MS patients and highlights the need to recognize their burden so that appropriate measures can be implemented.