OBJECTIVES:  To summarize trends in published literature regarding real-world evidence (RWE) for disease-modifying drugs (DMDs) in patients with multiple sclerosis (MS). METHODS:  A systematic search of peer-reviewed studies published from 2010 to 2016 using the PubMed database was conducted. Studies evaluating RWE (prospective [cohort studies, registries, case studies/series, surveys, or randomized naturalistic trials] and retrospective [administrative claims, electronic health record, and chart reviews] studies) were included. Search terms used were: multiple sclerosis AND (disease modifying OR interferon OR peginterferon OR glatiramer OR fingolimod OR teriflunomide OR dimethyl fumarate OR natalizumab OR mitoxantrone OR alemtuzumab OR daclizumab) AND (cohort OR observational OR retrospective OR database). The search was restricted to articles published in English. Publications that did not report primary data were excluded. RESULTS:  A total of 882 articles were identified using the search strategy; 313 were excluded (69 not evaluating MS, 70 not evaluating DMDs, 45 reviews/editorials, 37 pre-clinical/clinical studies, 35 study design/methodological studies, 33 meta-analyses, and 24 models). Two-thirds (68.4%) of the studies were prospective and one-third (31.6%) were retrospective. DMD types included were: self-injectables only (36.4%); orals only (6.7%); infusion therapies only (26.4%); self-injectables and orals (1.8%); self-injectables and infusion therapies (7.4%); orals and infusion therapies (2.8%); or self-injectables, orals, and infusion therapies (18.6%). Most studies were comparative (69.1% vs 30.9% noncomparative). Outcomes evaluated included relapses (44.6%), disease/disability progression (39.7%), safety/tolerability (32.0%), biomarkers (24.8%), brain activity (21.1%), adherence (19.7%), patient-reported outcomes (17.0%), resource use (6.9%), and cost (4.6%). From 2010 to 2016, the annual number of studies increased from 47 to 130. The proportion from Europe increased from 51.1% to 60.8%, whereas the proportion from the US decreased from 38.3% to 21.5%. CONCLUSIONS:  The prominence and types of RWE studies examining DMDs in MS is growing; additional research is needed to determine the quality of studies and the impact on decision making.