OBJECTIVES: Comorbidities in individuals with MS add to the complexity of disease management. A better understanding of the nature and prevalence of comorbid illness in MS may improve patient outcomes. The objective of this research was to gain a better understanding of the comorbid illnesses present in individuals with MS compared to individuals without MS. METHODS: The National Health and Wellness Survey (NHWS) is an Internet-based annual study of the healthcare attitudes and behaviors of a US representative adult sample.  Demographics and comorbidities were compared between individuals with diagnosed MS and individuals without MS. RESULTS: Compared to subjects without MS, a greater proportion of subjects with MS reported being female (64.3% vs. 51.3%; p<0.001) and being white (non-hispanic) (78.7% vs. 74.0%; p=0.006). Subjects with MS reported more comorbidity compared to subjects without MS (Charlson Comorbidity Index: 0.97 vs. 0.82; p<0.001). Neurologic symptoms and conditions (pain 56.7% vs. 37.8%, headache 55.8% vs. 44.6%, migraine 29.5% vs. 16.4%, restless leg syndrome 18.7% vs. 7.8%, and stroke 5.2% vs. 1.4%; p<0.001), and psychiatric symptoms and conditions (sleep difficulties 43.3% vs. 29.6%, depression 39.7% vs. 23.5%, anxiety 33.0% vs. 22.6%, insomnia 28.5% vs. 17.8%, and panic disorder 8.2% vs. 3.6%; p<0.001) were more common in subjects with MS compared to those without MS. Rates for hypertension (33.6% vs. 32.8%; p=0.968) and high cholesterol (32.3% vs. 30.9%; p=0.669) were similar but cardiovascular conditions such as angina (4.8% vs. 2.9%; p<0.001), arrhythmia (4.8% vs. 2.7%; p=0.003), and peripheral arterial disease (3.7% vs. 1.4%; p<0.001) were higher for MS subjects. CONCLUSIONS: As expected, individuals with MS have significant comorbid illness compared to individuals without MS. Neurologic and psychiatric conditions and symptoms are common and typically more prevalent in MS. Cardiovascular risk factors are similar to individuals without MS but higher rates of cardiovascular conditions were observed.