OBJECTIVES: To determine the frequency and economic impact of comorbid cardiac conditions among hospitalizations of patients with a diagnosis of multiple sclerosis (MS). METHODS: A retrospective analysis was conducted using the National Inpatient Sample (NIS), Healthcare Cost and Utilization Project, Agency for Healthcare Research and Quality. All hospital discharges with an MS diagnosis (ICD-9 CM 340.xx) from 1/1/2009 to 12/31/2009 were identified. Two cohorts were defined based on the presence or absence of at least one cardiac condition using ICD-9-CM codes: myocardial infarction (410.xx), ischemic disease (411.xx), angina (413.xx), occlusion of cerebral arteries (434.xx), acute cardiovascular disease (436.xx), cerebral ischemia (435.xx), and heart failure (428.xx). Total mean charges were converted to costs using NIS 2009 cost-to-charge ratios. Total costs per discharge were compared between cohorts while controlling for demographics, number of chronic comorbidities, and length of stay (LOS).  Descriptive statistics, t tests, and chi square tests were conducted where appropriate, and regression models were employed for cost comparisons. An incremental cost effectiveness ratio (ICER) was calculated for the cost per additional hospital day. RESULTS: A total of 27,463 discharges with a diagnosis of MS were identified, and 9.1% (n=2,522) had at least one cardiac comorbidity. The sample was 70% female with a mean age of 53.5 years. MS discharges with a cardiac condition were for patients with a significantly higher mean age (62.5 vs 50.5 years, P<0.0001), more chronic comorbidities (7.8 vs 4.7 conditions, P<0.0001), and a longer LOS (6.4 vs 5.2 days, P<0.0001).  The cost of hospitalization was significantly higher for MS discharges with a cardiac comorbidity after controlling for confounders ($16,752 vs $10,549, P<0.0001). The incremental cost per hospital day was $5,375 for discharges with a cardiac condition. CONCLUSIONS: Cardiac comorbidities are prevalent among MS discharges and are associated with higher costs than discharges without a cardiac comorbidity.