Objective: To assess the relationship between changes in patient-reported QoL, disease level and functional status after three months on natalizumab (TYSABRI). Methods: MS patients who received their 3rd natalizumab infusion and were enrolled in the manufacturer's restricted distribution program (TOUCH), participated in a 20-minute cross-sectional internet or telephone survey. Outcome measures included overall quality of life (QoL) change since initiating natalizumab using a 3-point scale (1-worse, 2-no change, 3-better), and pre/post disease level and functional status change. Disease level was measured on a 7 point scale: 0-“normal with no limitations on activity” through 6-“wheelchair bound” whereas functional status was measured on a 5 point scale: 1-“able to carry out usual daily activities” through 5-“required assistance”. Paired and independent sample t-tests were used based on the outcome metric. Results: Results from 319 patients in this ongoing survey (expected n=400) indicated that 75% were female. Overall QoL improved among 47% of patients, even in the short time on natalizumab. Only 3% of patients reported a worsening in QoL. On average, these patients were diagnosed with MS 15 years ago compared with the sample mean of 11 years. Increases in mean disease level change scores (0.30±1.13, p<0.001) and functional status change scores (0.36±0.80, p<0.001) were reported, indicating significant improvements. Compared to patients reporting no change or worsening QoL, patients reporting improved QoL had significantly higher mean disease change scores (0.56±1.28 vs. 0.08±0.92, p<0.001) and functional status change scores (0.71±0.82 vs. 0.04±0.63, p<0.001). Conclusion: After three months on natalizumab, patients reported improvements in overall QoL, disease level and functional status. These outcomes were positively and significantly associated with one another suggesting that, in a real world setting, patients may begin experiencing improvements in disease progression and QoL as early as three months after natalizumab initiation.