OBJECTIVES: We investigate the impact of recurrent relapses on short- and long-term healthcare costs in the United States. Relapses in multiple sclerosis (MS) are a major burden on patients' welfare and related healthcare costs, and have been shown to impact residual disability. While relapse costs have been reported previously, no publication has examined the impact of recurrent relapses on total healthcare costs. METHODS: We used medical (International Classification of Diseases-9 diagnoses) and pharmacy claims from a large, US National Health Plan database to identify MS patients with >=1 relapse who had enrolled in the plan between 2002-2004, and who had continuous enrolment 6 months pre- and 12 months post-index relapse. Costs were estimated based on claim charges, and were adjusted to project the amount in 2005 US dollars. Analyses were stratified by newly or previously diagnosed patients, and the number of relapses. Costs are presented in 90-day intervals in reference to the index relapse period (days 0-30). RESULTS: Newly diagnosed patients with >=2 relapses had higher monthly costs compared with patients with 1 relapse only at days 0-30 (index relapse) ($26,890 vs $16,121), 31-90 ($3,597 vs $1,506), and 271-360 ($3,768 vs $1,074). Although previously diagnosed patients with >=2 relapses had costs similar to those of patients with 1 relapse only at index relapse at days 0-30 ($21,350 vs $21,015), monthly costs were higher for patients with >=2 relapses at days 31-90 ($3,792 vs $2,712) and remained higher at days 271-360 ($3,636 vs $1,676). Monthly costs were generally higher for previously diagnosed patients with the exception of the acute phase of relapse (days 0-30) in the >=2 relapses subset. CONCLUSION: Recurrent relapses are associated with increased costs, both in the acute phase of managing a relapse and during the follow-up year in both newly diagnosed and previously diagnosed patients.