OBJECTIVES: Prolonged-release (PR) fampridine tablets (dalfampridine extended release in US) improve walking in some patients with multiple sclerosis (MS). The ENABLE study assessed the effect of long-term PR-fampridine treatment on health-related quality of life (HRQoL) in MS patients with walking impairment. METHODS: ENABLE is an open-label, 48-week study to evaluate the effect of PR-fampridine 10 mg twice daily on HRQoL in MS patients. Patients completed the Timed 25-Foot Walk (T25FW) at baseline and Weeks 2 and 4, and the 12-item MS Walking Scale (MSWS-12) at baseline and Week 4. Patients with any improvement in T25FW speed at both Weeks 2 and 4, and any improvement in MSWS-12 score at Week 4 remained on treatment. HRQoL measures are assessed at baseline and Weeks 12, 24, 36, and 48, and include the Short-Form Health Survey (SF-36), Multiple Sclerosis Impact Scale (MSIS-29), and the Patient Reported Indices for MS Activity Limitations Scale (PRIMUS ALS). The primary endpoint is the change from baseline in the SF-36 physical component summary (PCS) score at each visit in patients on treatment. RESULTS: At Week 4, 704 patients (78.1% of total enrollment [N=901]) met the criteria to remain on treatment. Interim results at 36 weeks in patients on treatment show improvement from baseline (mean change [95% CI]) in MSIS-29 Physical scores to Week 12 (-12.99 [-14.24, -11.74; P<0.0001], n=672) and Week 36 (-9.50 [-10.97, -8.04; P<0.0001], n=584). PRIMUS ALS scores also improved from baseline (mean change [95% CI]) to Week 12 (-2.47 [-2.83, -2.11; P<0.0001], n=501) and Week 36 (-1.53 [-1.96, -1.10; P<0.0001], n=437) in patients on treatment. Results for the change from baseline to Week 48 for outcomes, including the SF-36 PCS, in patients on treatment will be presented. CONCLUSIONS: PR-fampridine, which improves walking in MS, shows benefits on HRQoL through 36 weeks of treatment.