OBJECTIVES: To assess the cost utility and 5-year budget impact of one-time onasemnogene abeparvovec (formerly AVXS-101) versus current standard-of-care (chronic nusinersen) in spinal muscular atrophy type 1 (SMA1) patients in the United States (US). METHODS: We developed a multi-state survival Markov model with health-state transitions based on milestone attainment from published clinical trials. Survival benefit was estimated using long-term survival and natural history data. Eligible population size and expected market share were estimated using published sources. Costs were sourced from published claims analysis data, literature, and expert opinion. Utilities were from the CHERISH trial (NCT02292537). RESULTS: Undiscounted quality-adjusted life-years (QALYs)/patient were 30.3 for onasemnogene abeparvovec and 7.2 for nusinersen (discounted 3%: 15.9 and 5.3, respectively). Estimated discounted lifetime costs/patient were $6.33M for nusinersen and $3.7–4.7M for onasemnogene abeparvovec ($2–3M price points), resulting in cost savings and QALY gains (undiscounted, up to 57.5 QALYs; discounted 3%, 21.9 QALYs), implying onasemnogene abeparvovec was dominant. For US payers covering 1,000,000 individuals/year, 0.68 SMA1 patients would be treated annually. At a placeholder cost of $2M, the 5-year per-member-per-month (PMPM) budget impact of adding onasemnogene abeparvovec to the formulary was $0.05 ($3M: $0.11), decreasing each year, with an estimated offset of −$11K in SMA care costs in year 5. Installment plans will reduce the budget impact further. CONCLUSIONS: Onasemnogene abeparvovec is cost-effective compared to nusinersen, with potential to offset payers’ SMA care costs by year 5. Because discounting QALYs (3%) substantially underestimates health benefits, we recommend that US-based decision makers also consider undiscounted QALY gains when assessing innovative therapy value.