OBJECTIVES: To evaluate MS-related healthcare resource utilization and costs prior to and after initiating natalizumab in the US. METHODS: A retrospective administrative claims analysis was conducted using the Truven Health MarketScan Commercial and Medicare supplemental databases to identify adults diagnosed with MS (ICD-9-CM 340) who initiated natalizumab between January 1, 2007 and December 31, 2010 (first claim is the index date). Patients had ≥24 months of continuous enrollment (12 months before [pre-period] and 12 months after [post-period] the index date) and remained on natalizumab for the 12 month post-period. Patients with and without other disease modifying treatment (DMT) during the pre-period were examined. Patient characteristics, MS-related inpatient stays and corticosteroid use were described in the pre- and post-periods. RESULTS: The 1,458 patients in this study had a mean age of 45.2 years (standard deviation 10.5) and 74% were female.  The majority (70.1%) used a DMT during the pre-period.  After initiating natalizumab, there was a significant reduction in percentage of patients with MS-related inpatient stays (7.6% vs. 2.4%, p<0.001), MS-related inpatient costs (median $12,078 vs. $9,784, p<0.001) and length of stay (7.12 days vs. 6.26 days, p=0.005).  Reduction in percentage of patients with MS-related inpatient stays and costs were numerically higher for patients without DMTs in the pre-period (-6.2% and -$1,496 respectively) compared with those with a DMT in the pre-period (-4.8% and -$1,262, respectively).  Compared to the pre-period, there were significant reductions in IV and oral corticosteroid use for natalizumab initiators (-60.1% and -52.9%, respectively, p<0.001 for both). These reductions correspond to a mean corticosteroid cost per patient reduction of $101 across all natalizumab users (p<0.001). CONCLUSIONS: The initiation of natalizumab was associated with significant decreases in MS-related inpatient stays and corticosteroid use with corresponding decreases in length of stay and costs among natalizumab users with and without DMTs in the prior year.