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Background: Orthopedic pain is diagnosed and treated as a global health problem. Therapeutic interventions can change the behavior of patients and improve their quality of life. This study was aimed to evaluate the effectiveness of acceptance and commitment therapy (ACT) on illness perception among orthopedic patients., Materials and Methods: This quasi-experimental study was conducted as a two-group design (one experimental group and one control group) with pretest and posttest. Participants were selected from patients referred to the Mooud Physiotherapy Center in Mashhad, Iran. Patients were randomly divided into experimental and control groups (12 in each group). The experimental group received weekly sessions for three months (eight sessions), whereas the control group did not receive any intervention. Data were collected through Weinman's Illness Perception Questionnaire (with Cronbach's alpha coefficient of 0.72). Data were analyzed using multivariate analysis of covariance (MANCOVA)., Results: The results of the study showed that in terms of time, the outcome, and the meaning of disease, the patients in the ACT group had a lower mean in the posttest. Patients of the ACT group in personal and therapeutic controls showed a higher mean in the posttest than those of the control group. Therefore, ACT had a significant effect on improving the understanding of disease in orthopedic patients ( P < 0.05)., Conclusion: Based on the results, ACT has a significant effect on the disease perception of orthopedic patients. Therefore, it is suggested that therapists use this therapy approach to illness perception in orthopedic patients., Competing Interests: There are no conflicts of interest., (Copyright: © 2023 Journal of Education and Health Promotion.)