OBJECTIVES: Examine medication side-effects and patients' adherence to disease modifying medications. METHODS: A two-wave Internet survey was conducted by Harris Interactive among patients with multiple sclerosis in 2006, and 332 subjects from the first wave were analyzed (response rate 31%). RESULTS: Respondents were generally satisfied with the effectiveness of therapy, reporting 5 ± 1.0 (mean ± standard deviation) with 6 the most satisfied. Over half of subjects (53.8%) reported experiencing side effects. Frequent side effects were head/muscle ache (36.8%), injection site reaction (31.9%), fatigue (26.3%), fever (18.4%), pain (15.2%) and depression (10.5%). The majority of side effects began <1 day after starting therapy: 81.8% of head/muscle ache, 59.3% of site reaction and 56.7% of fatigue began in <1 day. The majority of fever (74.6%) lasted <1 day. The median duration of injection site reaction was 3 days, head/muscle ache was 1 day, and fatigue was 1 day. Over one-third (36.6%) of subjects reported forgetting (Horne scale) to take disease-modifying agents. CONCLUSION: Patients commonly reported side effects due to their therapy with disease modifying agents. This study provides a foundation for future research of determinants of MS patients' adherence behavior.