Background: Magnetic resonance imaging (MRI) guidance offers several theoretical advantages over computed tomography (CT) guidance in the context of stereotactic body radiotherapy (SBRT) for intact prostate cancer. Here we report the results of an interim analysis of the phase III MIRAGE trial, which directly compared MRI- and CT-guidance with a pragmatic primary endpoint of acute grade ≥2 genitourinary (GU) toxicity. Methods: MIRAGE is a single center, randomized phase 3 trial. Men undergoing SBRT for localized prostate cancer were randomly assigned to either CT-guidance or MRI-guidance. Planning margins of 4 mm (CT-arm) and 2 mm (MRI-arm) were placed around the prostate and proximal seminal vesicles, and this volume received 40 Gy in five fractions. Elective nodal radiotherapy and rectal spacers were allowed per physician discretion. The primary outcome was the incidence of acute (i.e., within 90 days of SBRT) grade ≥2 GU physician-reported toxicity (by CTCAE version 4.03). Secondary outcomes of interest included the incidence of acute grade ≥2 GU physician-reported toxicity, changes in IPSS scores at 1 and 3 months, and changes in EPIC-26 bowel domain summary scores at 1 and 3 months. A pre-specified efficacy analysis was planned once the 100^th patient was eligible for evaluation of the primary endpoint. Results: On 9/1/2021, 100 patients became eligible for evaluation for the interim analysis (51 CT arm, 49 MRI arm). Acute grade ≥2 GU toxicity was significantly reduced in men receiving MRI-guided SBRT (incidence of 24 (47.1%) vs. 11 (22.4%), p = 0.01). Acute grade ≥2 GI toxicity was also significantly reduced in men receiving MRI-guided SBRT (incidence of 7 (13.7%) vs. 0 (0%), p = 0.01.). The increase in IPSS scores from baseline was significantly higher in men receiving CT-guided SBRT at 1 month post-SBRT (median change of 10 vs. 6, p = 0.03), but not at 3 months (median change of 3 vs. 2, p = 0.3). The decrement in EPIC-26 bowel domain scores was significantly greater at 1 month in men receiving CT-guided SBRT (median change of -8.3 vs. 0, p = 0.03), but not at 3 months (median change of -2.3 vs. 0, p = 0.4). Given the large primary endpoint signal seen, our protocol was amended to reduce the projected sample size to 154 while still maintaining 89% power to detect a difference. Conclusions: This interim analysis demonstrates a statistically significant reduction in acute grade ≥2 GU toxicity with MRI-guidance versus CT-guidance in the context of prostate SBRT. Patient-reported urinary and bowel function metrics are also better preserved at the 1 month time point with MRI-guidance, though this difference dissipates (potentially due to side-effect management) at the 3 month time point. Accrual has been completed as of October 2021 and a final analysis for the primary endpoint is anticipated in early 2022. Clinical trial information: NCT04384770.