Infertility is one of the main problems of the family and is one of the factors that determine the identity and personality of Iranian infertile women. Family-centered empowerment model is a step toward increasing the self-efficacy of patients and enabling them to take responsibility of their illness. This study aimed to determine the effectiveness of applying family-centered empowerment model on irrational thoughts of Iranian infertile women. This study was a randomized clinical trial conducted on 80 infertile women and their husbands that were randomly divided into two intervention and control groups. Irrational Parenthood Cognitions questionnaire was given to the intervention and control groups to complete before and 3 months after the intervention. Data were analyzed using SPSS Statistics for Windows, version 13.0 (SPSS Inc., Chicago, IL, USA). The mean (SD) of irrational thoughts' scores in the control group before and after the study were 33.92 (5.98) and 33.20 (6.83) respectively, and in the intervention group were 34.55 (5.61) and 19.97 (3.52), respectively. The result of independent t-test showed a significant reduction in irrational thoughts of women in the intervention group after the family-centered empowerment model intervention. The family-centered empowerment model after three months of continuous implementation was able to effectively reduce the irrational thoughts about having children in infertile women.