OBJECTIVES To compare 6-month persistence rates among patients initiating the oral multiple sclerosis (MS) disease-modifying therapies (DMTs) fingolimod and dimethyl fumarate (DMF).  METHODS Our retrospective analysis used mail-order pharmacy claims from the US open-source LRx™ database (IMS). Patients with ≥1 fingolimod or DMF prescription (index DMT) between 01-April-2013 and 31-July-2013 were included. Patients were ≥18 years old, naive to fingolimod and DMF, and had not received multiple DMTs on the date of the first index DMT claim (index date). Prescription records were collected from pharmacies supplying ≥1 index DMT claim between the index date and the last month of follow-up. Persistence was assessed as time from initiating index DMT until discontinuation (gap of ≥60 days), receipt of another DMT or the end of the 6-month follow-up period. The risk of and time to index DMT discontinuation was assessed using a Cox proportional hazards model (controlling for age, gender and region) and Kaplan-Meier analysis, respectively.  RESULTS The study included 9546 patients (fingolimod: n=1390; DMF: n=8156). The proportion of patients discontinuing index DMT was significantly lower for patients receiving fingolimod (23.3%) versus DMF (36.6%; p<0.0001). The risk of discontinuation was 1.6-fold higher in the DMF cohort versus the fingolimod cohort (hazard ratio, 95% confidence intervals: 1.58, 1.41-1.77; p<0.0001). Time to discontinuation was significantly longer with fingolimod than with DMF (p<0.0001), resulting in a longer duration of therapy persistence for fingolimod versus DMF (mean ± standard deviation: 152±53 days versus 135±62 days, respectively). Results were similar when discontinuation was defined as a gap of ≥30 days (p<0.0001 for all outcomes).            CONCLUSIONS This analysis provides the first insight into short-term persistence rates with oral DMTs. In a real-world setting, the risk of discontinuation over 6 months was lower for patients initiating fingolimod versus DMF.