OBJECTIVES: In March 2019, onasemnogene abeparvovec (formerly AVXS-101) was evaluated by the Institute for Clinical and Economic Review (ICER) for cost-effectiveness and budget impact in the United States (US). While ICER did not make direct comparisons to nusinersen in the base case, it concluded that both onasemnogene abeparvovec and nusinersen have A-grade evidence ratings (high certainty of superiority over best supportive care). ICER used identical inputs for a common comparator which makes direct comparison possible. We conducted a post-hoc analysis to assess the cost-effectiveness and budget impact of onasemnogene abeparvovec versus nusinersen. METHODS: We used total lifetime cost and quality-adjusted life-years (QALYs) published by ICER for each treatment to make a direct comparison between onasemnogene abeparvovec and nusinersen (cost/QALY). ICER used a Markov model with health states based on ventilatory dependence and motor milestone achievement. We also estimated the ceiling price at which onasemnogene abeparvovec would remain under the 5-year budget impact threshold established by ICER ($991M). RESULTS: At a placeholder price of $2M (single dose), the average lifetime cost for onasemnogene abeparvovec is $3.657M compared with $3.884M for nusinersen, while onasemnogene abeparvovec delivers 12.23 QALYs compared with nusinersen’s 3.24. The cost/QALY is −$25,250, with onasemnogene abeparvovec being dominant. The budget impact of adding onasemnogene abeparvovec to the formulary of a payer in the US would be <$991M if the onasemnogene abeparvovec price is <$2.915M. At this price, the incremental cost-effectiveness ratio would be $76,529 (cost-effective using US thresholds). CONCLUSIONS: Using the independent ICER model, onasemnogene abeparvovec is dominant against nusinersen at the placeholder price of $2M and would have acceptable budget impact and cost-effectiveness at a price up to $2.915M.