12128 Background: Nasopharyngeal carcinoma (NPC) is a common disease in Southern China and Southeast Asia. Radiotherapy is an essential treatment for locoregionally advanced NPC (LA-NPC). Although Enhanced Recovery After Surgery (ERAS) is widely used in surgical settings, the guidelines do not systematically address the specific roles of various disciplines involved in radiotherapy rehabilitation. Therefore, we propose the concept of Enhanced Recovery After Radiotherapy (ERAR), which is considered to be a vital complement to radiology. Methods: We enrolled patients with stage III to IVA LA-NPC in this study. Participants completed baseline surveys before random assignment. ERAR interventions were implemented during radiotherapy to develop systematic management plans in the aspects of nursing, oral care, psychology, rehabilitation, nutrition, and skin health. The control group received conventional radiotherapy. Outcomes were evaluated at the 17th and 33rd radiotherapy sessions. We used generalized estimating equations to evaluate group by time effects on the outcomes, controlling for key covariates. Results: A total of 108 LA-NPC patients with a mean age of 48.3 ± 11.0 years were enrolled in the study group from August 2021 to September 2023. Across all time points, the ERAR group showed significant improvements in Hospital Anxiety and Depression Scale (HADS) anxiety ( P <.001), HADS depression ( P <.001), distress thermometer ( P =.049), quality of life ( P =.014), NRS2002 ( P =.040), weight loss ( P <.001), and Oral Health Impact Profile-14 (OHIP-14) ( P =.040) scores compared with the conventional care group. Conclusions: The ERAR pathway has a significant benefit on reducing acute radiation-induced toxicity in patients with LA-NPC. It is hoped that this study will provide a reference for clinicians and promote the implementation of a standardized protocol for rapid recovery from radiotherapy. Clinical trial information: ChiCTR2300075874. [Table: see text]