OBJECTIVES:  To evaluate the relationship between adherence to disease-modifying drugs (DMDs) and out-of-pocket costs in patients with multiple sclerosis (MS). METHODS:  Data were obtained from a sample of patients with MS (n=1112) from the US National Health and Wellness Survey and Lightspeed Research panel and its affiliates. Patients completed a 30-minute Internet survey between April and October 2015. The survey included questions about demographics, disease severity, symptoms, comorbidities, treatments, and monthly out-of-pocket costs. Patients indicating current DMD treatment were included. Adherence was evaluated using the 4-item Morisky Medication Adherence Scale (MMAS-4). MS-related monthly out-of-pocket costs, including doctor visit costs, medication costs, and other costs, were summed to provide a monthly estimate for MS-related out-of-pocket total costs. RESULTS:  Of 805 survey respondents meeting study criteria, 429 (53.3%) reported high adherence (MMAS-4 score = 0), 309 (38.4%) moderate adherence (MMAS-4 score = 1 or 2), and 67 (8.3%) low adherence (MMAS-4 score = 3 or 4). Those with low adherence reported the highest mean monthly MS-related out-of-pocket doctor visit costs ($42.60 vs moderate [$23.75] and high adherers [$24.07]; p<0.05), and the highest mean monthly MS-related out-of-pocket other costs ($71.37 vs moderate [$42.34] and high adherers [$35.57]; p<0.05). Mean monthly MS-related out-of-pocket medication costs were numerically higher in low adherers, but differences were not statistically significant ($86.37 vs moderate [$53.77] and high adherers [$64.25]; p=0.555). Mean monthly MS-related out-of-pocket total costs were also numerically higher in low adherers, but differences did not reach significance ($200.34 vs moderate [$119.86] and high adherers [$123.89]; p=0.095). CONCLUSIONS:  In this study, patients with MS with low adherence to DMDs had significantly higher mean monthly MS-related out-of-pocket doctor visit and other costs compared with patients with moderate or high adherence. Further research is needed to better understand the barriers to DMD adherence and how improved adherence may impact monthly MS-related out-of-pocket costs.