Abstract Introduction Sexual health toxicities remain an under-reported but important health outcome for patients undergoing radiotherapy for localized prostate cancer. With the increasing adoption of higher daily doses of radiation over shorter timeframes delivered using stereotactic body radiotherapy (SBRT), the precision of radiation delivery remains an important factor that can reduce patient toxicity. MRI-guided SBRT (MRgRT) allows for improved image quality, treatment gating, and planning target volume margin reduction, offering improved radiation precision, which may translate to reduced treatment-related toxicity as compared to traditional CT-guided SBRT (CTgRT). Objective We sought to evaluate the effect of MRI-guidance on sexual health toxicity in patients following prostate SBRT for the treatment of localized prostate cancer. Methods We conducted a post-hoc analysis of patients enrolled on a phase III single-center randomized trial (MIRAGE: NCT04384770). The trial overall seeks to study the relative benefit of MRI vs CT guided SBRT (40 Gy/5 fractions) in patients with localized prostate cancer. Right and left neurovascular bundles (NVBs) and internal pudendal arteries (IPAs) were contoured on treatment planning images. Dosimetric parameters for these structures (Dmax, Dmin, Dmean, and V20Gy) were collected. Patient-reported sexual function outcomes (SHIM and EPIC-26 surveys) were also collected prior to treatment and at 1, 3, and 12 months following treatment. A clinically relevant decrement was defined as a ≥24 point decrease in the EPIC-26 sexual domain scores and a ≥9 point decrease on SHIM surveys. Unpaired t-tests and chi-square tests were used to evaluate for statistical significance. Results 152 patients received either MRgRT (n = 77) or CTgRT (n = 75). MRgRT resulted in a significant improvement in the volume receiving 20 Gy or less of radiation (V20Gy) in the left NVB (7.3cc vs 10.9cc, p = 4.4x10-8), right NVB (7.0cc vs 10.7cc, p = 2.8x10-7), and right IPA (0.42cc vs 1.35cc, p = 0.049), and trended towards significance for the left IPA (0.3cc vs 1.1cc, p = 0.066). Only 48 patients were not given hormonal therapy with radiotherapy. No statistically significant differences in clinically relevant decrements in patient-reported SHIM or EPIC scores were seen between MRgRT and CTgRT in these patients. No clear association between acute or chronic (12-months post-RT) sexual health toxicity and radiation exposure to the NVBs or IPAs was identified. Conclusions Patients treated with MRgRT had decreased radiation exposure to the bilateral NVBs and IPAs compared to patients treated with CTgRT. These data highlight the dosimetric benefits of MRgRT with regard to sexually relevant organs at risk. Power to detect associations between dosimetry and patient-reported sexual health outcomes will increase as the data matures and more patients have recovered testosterone after use of hormonal therapy. Future work will assess the impact on MRI-guided vs CT-guided radiation on sexual health outcomes at later time points. Disclosure No.