Aims reSET-O is a Food and Drug Administration-cleared prescription digital therapeutic (PDT) indicated to improve outpatient-treatment retention of patients with opioid use disorder (OUD). This study examined the cost-effectiveness and budget impact of reSET-O in conjunction with treatment as usual (reSET-O+ TAU) relative to TAU. Materials and methods Adult patients with≥ 1 OUD diagnosis, treated with buprenorphine from 1 January 2015 to 30 March 2018, were identified from Truven Health MarketScan Commercial and Medicare Supplemental Research Databases. Twelve-week healthcare resource utilization (HCRU) costs for patients categorized as adherent and nonadherent to buprenorphine treatment were estimated. Total 12-week costs included OUD treatment and other HCRU costs. The cost-effectiveness of reSET-O+ TAU was modeled in accordance with prior clinical trial outcomes. The 12-week budget impact of reSET-O was modeled for a 1 million-member healthcare plan. Results Higher buprenorphine adherence was associated with lower HCRU costs in claims data. Twelve-week per-patient total costs were 305moreforthosereceivingreSET-O+TAUthanthosereceivingTAU.Theincrementalcost-effectivenessratiowas 18.70 per 1 percentage-point increase in the treatment retention rate. The probability that reSET-O+ TAU would be considered cost-effective was over 92% for willingness-to-pay thresholds of 6,000ormore.The12-weekbudgetimpactofreSET-Owas 8,908, translating to 0.003permemberpermonth.LimitationsThefindingsofthecost-effectivenessandbudgetimpactmodelingarelimitedbytheassumptionsofthemodelsduetouncertaintyaroundsomeinputs.Whilenomodelisfreeofbias,theinputsforthismodelwerecarefullyselectedtoreflectcontemporarytreatmentpatterns.ConclusionsDependingonthepayer’swillingnesstopay,reSET-Omaybecost-effectiveinincreasingbuprenorphinetreatmentretentionrates.reSET-Oresultsinanapproximatebudgetimpactof 0.003 per member per month, depending on market share and the prevalence of the population receiving treatment for OUD.