Background and purpose: To compare the cost-effectiveness of treating prostate cancer patients with intensity-modulated radiation therapy and a spacer (IMRT+S) versus IMRT-only without a spacer (IMRT-O). Materials and method: A decision-analytic Markov model was constructed to examine the effect of late rectal toxicity and compare the costs and quality-adjusted Life Years (QALYs) of IMRT-O and IMRT+S. The main assumption of this modeling study was that disease progression, genito-urinary toxicity and survival were equal for both comparators. Results: For all patients, IMRT+S revealed a lower toxicity than IMRT-O. Treatment follow-up and toxicity costs for IMRT-O and IMRT+S amounted to 1604 and 1444, respectively, thus saving 160 on the complication costs at an extra charge of 1700 for the spacer in IMRT+S. The QALYs yielded for IMRT-O and IMRT+S were 3.542 and 3.570, respectively. This results in an incremental cost-effectiveness ratio (ICER) of 55,880 per QALY gained. For a ceiling ratio of 80,000, IMRT+S had a 77% probability of being cost-effective. Conclusion: IMRT+S is cost-effective compared to IMRT-O based on its potential to reduce radiotherapy-related toxicity.