Objective: Increasing use of the prepectoral plane in postmastectomy implant-based reconstruction has made immediate direct-to-implant (DTI) reconstruction more achievable. There has also been an increased incidence of postmastectomy radiation therapy, making it important to understand the feasibility of immediate DTI reconstruction in patients who may require adjuvant radiation therapy. Methods: A retrospective cohort study of consecutive patients undergoing DTI prepectoral reconstruction with and without postmastectomy radiation was performed. Patient and treatment level factors, operative and post-operative outcomes were extracted on both the patient and breast level. The presence of at least one minor complication (superficial or full-thickness necrosis, cellulitis requiring oral antibiotics, hematoma, or seroma) or major complication (cellulitis requiring intravenous antibiotics, hospital re-admission, explanation, or unplanned return to the operating room) was compared. Univariate analysis was performed to evaluate differences in outcomes between groups. Results: From January 2018 to December 2021, 148 patients (240 breasts) underwent prepectoral DTI reconstruction. In this group, 125 patients (217 breasts) did not undergo postmastectomy radiation therapy, whereas 23 patients (23 breasts) were exposed to postmastectomy radiation therapy. Mean follow-up time was 218 days (+/- 196.8). There were no significant differences in demographics, operative time, implant type or size, mastectomy type, or mean operative time. Patients who underwent adjuvant radiation had higher rates of neoadjuvant chemotherapy (p<0.001) and axillary lymph node dissection (p<0.001). Univariate analysis did not demonstrate any significant differences in minor or major complications between the radiated and non-radiated breasts. Conclusion: While limited by a small number of patients who underwent radiation, postmastectomy immediate DTI reconstruction is a feasible and safe surgical option for patients to have a completed breast mound prior to radiation therapy. Corresponding Author: Jamie Hall MD, [email protected], 313-850-4148