Objective: To assess multiple sclerosis (MS) patient-reported experiences with natalizumab (TYSABRI) in a real-world setting. 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. Patient-reported measures included an adapted version of the Multiple Sclerosis Impact Scale-29 (MSIS-29), pre/post disease level and functional status scores and prior MS drug use. MSIS-29 responses were modified to measure patient-perceived change since initiating natalizumab. Paired t-tests assessed pre/post changes in disease level and functional status, where positive change indicated improvement. Results: Results from 319 patients in this ongoing survey (expected n=400) indicated that 75% were female and, on average, were diagnosed with MS over 11 years ago. Almost all (97%) patients used =1 MS drug before natalizumab. The most frequently used drugs were: interferon beta-1a (Avonex) (67%), glatiramer acetate (Copaxone) (49%), interferon beta-1b (Betaseron) (36%) and interferon beta-1a (Rebif) (35%). Despite the short treatment duration, there were significant improvements in disease level (0.30±1.13; t=4.78; p<0.001) and functional status (0.36±0.80; t=7.96; p<0.001). MSIS-29 items with greatest reported improvement since initiating natalizumab were: “worries related to MS” (66%), “feeling unwell” (64%), ability to do “physically demanding tasks” (63%), “problems with balance” (61%), “feeling mentally fatigued” (61%) and “difficulties moving about indoors” (60%). Items with least reported improvement were: “tremors of your arms or legs” (49%), “being stuck at home” (49%), “problems sleeping” (49%) and “problems using transport” (42%). On average, patients reported improvement on 13 of 29 (45%) MSIS-29 items. Conclusion: After only 3 months on natalizumab, patients reported improvements on MSIS-29 items, disease level and functional status. While preliminary, these early results are suggestive of natalizumab's beneficial effect on patients and warrant further long term investigation of its impact on patient outcomes in a real-world setting.