OBJECTIVES: Identify a population of multiple sclerosis (MS) patients new to treatment with natalizumab.  Observe and record healthcare costs before initiation of natalizumab and up to 3 years after continuing treatment. Compare and quantify differences in costs based on patterns of natalizumab use. METHODS: Using integrated medical and pharmacy claims data (IMS LifeLink™ Health Plan Claims and Longitudinal Prescriptions databases), patients were included in the analysis based on the presence of a diagnosis of MS (ICD-9 code 340.*) during calendar years 2005 through 2008. Economic information related to the treatment of MS was captured using the Episode Treatment Group™ software. RESULTS: From the database, 76 MS patients that started natalizumab treatment and had 4 full calendar years of data were observed. These patients were observed for the year prior to start of natalizumab treatment in 2006, through the end of the 2008 calendar year. Patients were stratified by continued use of natalizumab during the study period. For all patients, there were significant increases in annual pharmacy costs ($17,667 to $40,399) during the year natalizumab treatment was initiated, in addition to outpatient medical services ($8,383 to $11,744). For patients who continued natalizumab for the entire study period, inpatient costs decreased from $2,630 to an average of $5 per year; emergency room costs in this group also decreased from a maximum of $537 to $218 annually. For patients who discontinued natalizumab during the study period, there were increased inpatient costs after discontinuation ($2,630 to $6,701). CONCLUSIONS: Though the study size is small, the cost observations can enable decision-makers to better understand costs associated with the short and longer-term use of natalizumab for the treatment of MS.