Introduction: Recently, minimally invasive surgical therapies (MISTs) have become an alternative to surgery or pharmacotherapy to manage benign prostatic hyperplasia (BPH). This study evaluated the cost-utility of water vapor thermal therapy (WVTT) and prostatic urethral lift (PUL) compared to pharmacotherapy as initial treatment for patients with moderate-to-severe BPH. Methods: In this model-based economic evaluation we simulated BPH progression in men (mean age 65 years, average International Prostate Symptom Score 16.6) over their lifetime and estimated healthcare costs (from the Canadian healthcare payer perspective) per quality-adjusted life year (QALY), discounted at 1.5% annually. In the model, men could receive up to three lines of therapy: i) initial pharmacotherapy with MIST as second-line, and TURP or pharmacotherapy as third-line; ii) initial MIST (WVTT or PUL) with MIST again, TURP or pharmacotherapy as second-line, and TURP as third-line. The model was populated using data from the published literature. Results: The expected lifetime QALYs and costs were 15.50 QALYs and $14,626 for initial treatment with WVTT, 15.35 QALYs and $11,795 for pharmacotherapy followed by WVTT, 15.29 QALYs and $13,582 for pharmacotherapy followed by PUL, 15.29 QALYs and $19,151 for initial treatment with PUL. Strategies involving PUL procedures were dominated by strategies involving WVTT. The incremental cost per QALY gained was $18,873 for initial WVTT compared to initial pharmacotherapy followed by WVTT. Conclusion: WVTT appears to be a cost-effective procedure, and may be an appropriate first-line alternative to pharmacotherapy for patients with BPH who seek faster improvement and no lifelong commitment to daily medications.