OBJECTIVES: Adverse Drug Reactions (ADRs) and outcomes observed during homogenous pre-approval clinical trials frequently do not correlate with real-world experience. The substantial costs associated with ADRs and poor outcomes represent a significant burden to the healthcare system. Frequency estimates coupled with specific ADR and outcome costs may provide a way to compare downstream impact. This study sought to estimate the post-marketing costs associated with ADRs and outcomes for individual drugs by combining: 1) ADR and outcome-specific costs, 2) data from the FDA’s Adverse Event Reporting database (FAERS), and 3) drug usage information. METHODS: ADR and outcome data were obtained from FAERS. ADR and outcome costs were obtained from AHRQ. ICD-9 codes for ADR costs were mapped to MedDRA Preferred Terms with BioPortal and ICD9Data.com. Focus was limited to EudraVigilance Important Medical Event ADRs. Evaluate Pharma (evaluategroup.com) provided usage data. From January 2011 through December 2013, either the most costly “primary suspect” ADR or outcome cost was assigned to each case report. Individual report costs were summed for each drug and then divided by exposure rates to obtain downstream costs per patient. Eight drugs prescribed to treat multiple sclerosis (MS) were analyzed in detail. RESULTS: From lowest to highest, average downstream costs per patient exposed were: glatiramer acetate ($86); dalfampridine ($248); interferon beta-1b ($404); dimethyl fumarate ($552); fingolimod ($563); interferon beta-1a (Avonex) ($1,045); interferon beta-1a (Rebif) ($1,419); and natalizumab ($2,345). It should be noted that under reporting to FAERS may result in under estimation of the costs above. CONCLUSIONS: Post-marketing ADRs and poor outcomes represent a significant safety issue and cost burden for the healthcare industry. The method outlined here used post-marketing data and specific cost estimates to compare serious side effect costs across MS drugs. Future work may include analyzing other drug classes and using claims data for ADR and outcome frequency estimates.