OBJECTIVES: While many treatments exist for the relapsing form of multiple sclerosis (MS), there are none currently available for primary progressive MS (PPMS). In a phase III trial, ocrelizumab significantly reduced the proportion of patients who had 12-week confirmed disability progression compared to placebo in patients with PPMS.  The objective of this study was to determine the potential cost-effectiveness of ocrelizumab in PPMS patients compared to no active treatment. METHODS: A Markov model with a lifetime time horizon and quarterly cycles was developed from the payer perspective assuming a cohort of PPMS patients similar to those in the clinical trial. Utility and clinical inputs were obtained from the literature and from the ORATORIO trial. Each transition state represented a full point Expanded Disability Status Scale (EDSS) state. Medical costs were obtained from the literature.  As ocrelizumab is not yet on the market, the price was benchmarked and evaluated in threshold analyses. The results are presented for the incremental quality-adjusted life years (QALYs), incremental costs, and the incremental cost-effectiveness ratio (ICER).  Sensitivity analyses were performed to determine the robustness of the model. RESULTS: The model estimates that ocrelizumab improved QALYs by 8.97 vs. no treatment and increased costs by $1.35 million.  This yields an ICER for ocrelizumab of $150,485/QALY in the base case. To meet willingness-to-pay thresholds of $50,000/QALY and $100,000/QALY, the cost of medication would have to be around $18,348 and $33,840 annually, respectively. One-way sensitivity analysis showed that varying the drug costs influenced the ICER the most. CONCLUSIONS: The model suggests ocrelizumab could become a meaningful treatment option for patients with PPMS.  It may also be a cost-effective option depending on the launch price and willingness-to-pay threshold. In the base case scenario, the benchmarked cost of ocrelizumab was comparable to currently available branded MS medications.