Introduction: Acquisition of chronic diseases such as asthma leads to psychological, mental and physical complications in adolescents, and hence their self-esteem may be compromised. Therefore, the present study was conducted to assess the effect of Orem’s self-care model on self-esteem of adolescents with asthma. Materials and Methods: This semi-experimental study enrolled 64 asthmatic adolescents referred to Shariati Hospital, Isfahan. Subjects were assigned to two groups of control and intervention consecutively. Then, the self-care training program was conducted according to Orem’s self-care model in eight two-hour sessions based on self-care needs, and self-esteem was measured in the two groups prior to and two months after the last training session. The data were collected by a questionnaire of demographic characteristics and the Coopersmith Self-Esteem Inventories (CSEI) and analyzed by SPSS version 20. Results: Independent t-test showed a significant difference in the mean score of self-esteem between the intervention and control groups after the training (p <0.05), but the difference was not statistically significant prior to the intervention. Paired t-test showed a significant difference in the mean score of self-esteem before and after the training in the intervention group (p <0.01), but this difference was not statistically significant in the control group (P>0.05). Conclusion: Regarding the effect of Orem’s self-care model on self-esteem of adolescents with asthma, we recommend the use of this model as a care intervention in healthcare centers to promote adolescents’ health.