OBJECTIVES: To describe diagnosis codes, frequency and cost of multiple sclerosis (MS)-related hospital and emergency room (ER) utilization.  METHODS: Two cohorts of MS-diagnosed patients aged 18-64 years were selected from a national managed care database: 1) longitudinal cohort: patients with 12 months pre/post eligibility around first MS diagnosis occurring January 1, 2002 to July 30, 2010, and 2) cross-sectional cohort: patients with an MS diagnosis in 2010. MS-related [multiple sclerosis (ICD-9-CM=340.XX), other demyelinating CNS disease (ICD-9-CM=341.XX), and a group of symptom-related codes] hospitalizations and ER visits were evaluated. Rehabilitation (ICD-9-CM=V57.89) was included based on qualitative review of codes. Mean number and cost per patient, adjusted to $US 2010, were described.  RESULTS: There were 31,905 patients in the longitudinal cohort and 32,845 patients in the cross-sectional cohort. In the longitudinal cohort, 18.5% had a post-index hospitalization (any cause) with 5.2% being MS-related (340.XX: 3.2%; 341.XX: 0.4%; rehabilitation: 0.8%; and symptom-related: 1.1%). Mean number and cost (SD) of an MS-related hospitalization were 1.19 (0.55) and $14,358 ($32,356), respectively. In addition, 31.4% of patients experienced a post-index ER visit with 6.9% being MS-related (340.XX: 2.9%; 341.XX: 0.2%; symptom-related: 4.7%). Mean number and cost (SD) of an MS-related ER visit were 1.23 (0.78) and $573 ($816), respectively. In the cross-sectional cohort, 12.5% had a hospitalization (any cause) with 3.7% being MS-related (340.XX: 2.1%; 341.XX: 0.2%; rehabilitation: 1.1%; and symptom-related: 0.7%). Mean number and cost (SD) of an MS-related hospitalization were 1.32 (0.78) and $16,213 ($25,394), respectively. In addition, 27.3% of patients experienced an ER visit with 6.4% being MS-related (340.XX: 2.6%; 341.XX: 0.1%; and symptom-related: 4.5%). Mean number and cost (SD) of an MS-related ER visit were 1.37 (0.89) and $682 ($825), respectively. CONCLUSIONS: Costs for hospitalization and ER visits among MS patients were substantial. Inclusion of rehabilitation and symptom-related codes can account for an under-recognized proportion of expenditures.