OBJECTIVES: To assess patient-reported treatment satisfaction with natalizumab in MS patients in the United States (US). METHODS: MS patients initiating natalizumab were invited to participate in a longitudinal study.  Patients complete self-reported assessments prior to natalizumab initiation and then after the 3rd, 6th and 12th natalizumab infusions. As part of the baseline (BL) assessment, patients reported their satisfaction with MS drugs used prior to natalizumab initiation. For the follow-up assessments, patients reported their satisfaction with natalizumab treatment. Patient self-reported measures included satisfaction with treatment effectiveness, convenience of use, and global treatment satisfaction scales from the Treatment Satisfaction Questionnaire. Each scale consists of 3 items, with responses measured on a 7-point Likert Scale ranging from 1 (low) to 7 (high). Individual item responses are added and scores are transformed to a 0 to 100 scale with higher scores indicating higher satisfaction.  This analysis evaluates the change in satisfaction from baseline through the 6th natalizumab infusion after controlling for number of natalizumab infusions, age, years since MS diagnosis, baseline disease disability and functional status, comorbidity burden, and number of MS drugs used prior to natalizumab. RESULTS: Data from 296 patients indicated that 78% are female, the mean age is 47±11 years and the mean time since MS diagnosis is 11±9 years. Almost all (97%) patients used at least one other MS drug before natalizumab. After controlling for covariates, significant increases in effectiveness (BL 44.22±8.62, 3rd 61.91±6.87 and 6th 69.48±4.96, p<0.0001), convenience (BL 60.80±6.27, 3rd 79.18±3.25 and 6th 79.69±0.42, p<0.0001), and global satisfaction (BL 62.46±3.92, 3rd 75.36±3.92 and 6th 76.51±3.92, p<0.0001) were observed. CONCLUSIONS: Patients’ satisfaction with natalizumab increased with increasing treatment duration. Patients reported higher levels of satisfaction with treatment effectiveness, convenience of use, and global satisfaction while receiving natalizumab compared to their satisfaction levels with MS drugs received before initiating natalizumab.