Introduction: Variable costs of different radiation treatment modalities have played an important factor in selecting the most appropriate treatment for patients with intermediate-risk prostate cancer. Methods: Analysis using a Markov model was conducted to simulate 20-year disease trajectory, quality-adjusted life years (QALYs) and health system costs of a cohort of intermediate-risk prostate cancer patients with mean age of 60 years. Clinical outcomes on toxicity and disease recurrence were measured and a probabilistic sensitivity analysis was performed, varying input parameters simultaneously according to their distributions. Results: Among the six radiation treatment modalities, including conventionally fractionated intensity-modulated radiation therapy (IMRT), hypofractionated IMRT, IMRT combined with high-dose-rate (HDR) brachytherapy, HDR brachytherapy monotherapy, low-dose-rate brachytherapy monotherapy, and stereotactic body radiotherapy (SBRT), SBRT was found to be more cost-effective when compared with LDR-b and other treatment modalities, resulting in an incremental cost–utility ratio of $2985 per QALY. Conclusions: Stereotactic body radiotherapy is the most cost-effective radiation treatment modality in treatment of intermediate-risk prostate cancer, while treatment toxicity and cost data are the key drivers of the cost–utility. Further work is required with long-term follow-up for SBRT.