e13811 Background: MR-guided radiation therapy offers an innovative approach, providing superior soft tissue contrast that enables clinicians to deliver higher doses to the target site with fewer fractions. The objective of the study is to assess objective response rates and adverse effects related to a community-based single-institution experience with the ViewRay MRIdian. Methods: An IRB-approved registrational trial was conducted at the Providence Cancer Institute starting May 2020, with data cutoff of September 2023. All patients treated underwent MR screening, and the target site(s) were treated using hypofractionated radiation therapy in ≤5 fractions. The primary endpoint was to assess adverse effects attributed to radiation therapy. Secondary measures included local recurrence-free survival (LRFS), distant metastasis-free survival (DMFS), overall survival (OS), and change in prostate-specific antigen (PSA) for patients treated definitively for prostate cancer. The assessments were performed under the guidance of experienced radiation oncologists. Results: From May 2020 to September 2023, n=257 patients received treatment on the MRIdian with a median follow-up of 430 days [range 4-1221 days]. One and 2-year LRFS was 92% and 87%, and excluding prostate and breast cancer, 83% and 70%. Definitive prostatestereotactic body radiation therapy(SBRT) was delivered to 117 patients and significantly reduced PSA (mean difference -6.27, p<0.0001), with no local failures to date. One and 2-year DMFS was 75% and 67%, though if excluding definitive prostate SBRT and partial breast irradiation, these were 48% and 33%. The OS rate at 1 and 2 years was 86% and 76%. Excluding prostate and breast cancer, the 1 and 2-year OS was 74% and 55%. Grade 3+ adverse events possibly or definitely attributable to radiation therapy were noted in 5% (n=13/257) of patients, including 2 possible treatment-associated deaths (bowel perforation following liver SBRT, and respiratory failure following lung SBRT and trastuzumab-deruxtecan systemic therapy). Conclusions: Our institutional experience with the MRIdian demonstrated high levels of local control, while overall survival was driven by out-of-field failures. Serious adverse events were infrequent, but more common in abdominal targets highlighting the need for careful planning and tight organs at risk (OAR) constraints, particularly if systemic therapy is delivered soon after radiation.