Objectives: Inability to have a child is stressful and affects all aspects of couples’ lives. Infertility diagnosis, duration and reason of infertility, treatment failure, and frequent pregnancy tests are among the stress-inducing factors in couples. The current study aimed to compare infertility-related stress among couples and evaluate its relationships with infertility factors. Materials and Methods: This cross-sectional study was performed on 150 infertile couples (300 individuals) visiting infertility centers of Tehran. The data were collected using the Fertility Problem Inventory (FPI) and fertility and demographic characteristics form. The subjects were selected through convenience sampling method. The data were analyzed through inferential statistics, including paired samples t-test, independent samples t test, ANOVA, and linear regression. Results: According to the results, the mean stress score of women was significantly higher than that of the men (P=0.007). There was a significant difference between males and females regarding the mean scores of social concern and need for parenthood (P=0.005). The mean score of infertility-related stress was also significantly higher in women with treatment failure than in men (P=0.01). Conclusions: Based on the findings of the present study, infertile women experienced greater stress than males. Furthermore, infertility-related stress increased in women due to treatment failure. Therefore, it is recommended that women who have experienced treatment failure be subjected to precise psychological evaluations before undergoing the treatment process.