OBJECTIVE: Congenital hemophilia B is a rare bleeding disorder caused by defects in the gene encoding factor IX (FIX) leading to coagulation deficiency. Recurrent bleeds may cause chronic pain, disability, and reduced quality of life. Phase 2 b and 3 single-arm, open-label, single-dose trials assessing etranacogene dezaparvovec gene therapy for hemophilia B have demonstrated sustained FIX activity levels over observed periods, but long-term durability of the treatment effect has not been established. Using statistical modeling, we estimate long-term durability of FIX activity levels after receiving etranacogene dezaparvovec. METHODS: Participants from Phase 2 b ( = 3; NCT03489291) and 3 studies ( = 52; NCT03569891) were included. Two participants who did not respond to treatment were excluded. FIX activity was assessed by one-stage activated partial thromboplastin time assay. FIX activity levels at Month 6 post-treatment were considered baseline. Bayesian and Frequentist linear mixed models predicted FIX activity levels up to 25.5 years at an individual and population level with pre-treatment adeno-associated virus 5 (AAV5) neutralizing antibody (NAb) status as primary covariate. RESULTS: Bayesian and Frequentist linear mixed models predicted no more than 6/55 (10.91%) observed participants would have FIX activity levels <2% up to 25.5 years post-infusion. Bayesian model-based predictions of future participants suggest >80% would be free from prophylactic FIX replacement products 25.5 years post-infusion. Both models predicted FIX activity levels were not significantly influenced by pre-treatment AAV5 NAb status. CONCLUSIONS: People with hemophilia B receiving etranacogene dezaparvovec would likely achieve durable FIX activity levels and remain free of prophylactic FIX replacement products for up to 25.5 years following single administration. The long-term factor IX durability predictions are based on statistical methods and results may differ.