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Orientation and mobility (O&M) training is a practical and helpful method to prepare people who are blind for independent living. Hence, this study aimed to survey the effect of O&M training on the quality of life in students who are blind in Iran. This research was a quasi-randomized controlled trial design. Participants were 24 third-grade to sixth-grade students from two schools for blind in Isfahan, Iran. Using cluster sampling method, one school was assigned to the experimental group ( n = 12) and the other to the control group ( n = 12). The experimental group participated in the 8-session O&M training program. Both groups completed a World Health Organization Quality of Life (WHOQOL-BREF) at pre-intervention and post-intervention. The obtained data were analyzed using analysis of covariance (ANCOVA) and multivariate analysis of covariance (MANCOVA) test. The results showed significant increases in quality of life and all subscales (physical health, mental health, social relationships, and environmental health) in the experimental group than in the control group. The findings suggest that O&M training can promote quality of life among students who are blind in Iran. Moreover, these findings increase the interest of children and adolescents who are blind in O&M training.