Background Benign prostatic hyperplasia (BPH) is a disease that affects millions of U.S. men and is costly to treat. Purpose To compare the cost-effectiveness of four minimally invasive therapies (MITs) and medical management for the treatment of BPH. Materials and Methods A cost-effectiveness analysis from a payer's perspective with Markov modeling was performed, comparing prostatic artery embolization (PAE), prostatic urethral lift, aquablation, water vapor thermal therapy, and medical management for BPH spanning a time horizon of 5 years. The model incorporated the probability of procedural complications and recurrent symptoms necessitating retreatment, which were extracted from published studies with long-term follow-up. Costs were based on Medicare reimbursements using CPT codes for ambulatory surgery centers. Outcomes were measured using the quality-adjusted life year (QALY), incorporating both life quality and expectancy. Statistical analyses included a base case calculation (using the most probable value of each parameter) and probabilistic and deterministic sensitivity analyses. Results In the base case calculation, outcomes for the strategies were comparable, with a difference of 0.030 QALY (11 days of life in perfect health) between the most (PAE) and least (medical management) effective strategies. PAE was the most cost-effective strategy relative to medical management, with an incremental cost-effectiveness ratio of $64 842 per QALY. Probabilistic sensitivity analysis showed PAE was more cost-effective compared with prostatic urethral lift, aquablation, water vapor therapy, and medical management in pairwise comparisons. In sensitivity analysis of retreatment risk, PAE remained the most cost-effective strategy until its repeat treatment rates exceeded 2.30% per 6 months, at which point water vapor therapy became the optimal choice. PAE was the most cost-effective procedure when its procedural cost was lower than $4755. Aquablation and prostatic urethral lift became more cost-effective when their procedural costs were lower than $3015 and $1097, respectively. Conclusion This modeling-based study showed that PAE appears to be a cost-effective modality among medical management and MITs for patients with BPH, with comparable outcomes to prostatic urethral lift, water vapor therapy, and aquablation at a lower expected cost. © RSNA, 2023 Supplemental material is available for this article. See also the editorial by Gemmete in this issue.