Infertility can cause psychological distress and has a negative impact on quality of life (QoL). There have been no studies investigating the effect of depression on QoL in infertile couples at the dyadic level. This study aimed to investigate the effects of actors' and partners' depression on QoL in male-female dyads experiencing infertility using an innovative dyadic analysis approach, the Actor-Partner Interdependence Model (APIM).We conducted this cross-sectional study on 180 infertile couples in Tehran, Iran, during August-September 2017. Quality of life and depression were assessed using Fertility Quality of Life and Patient Health Questionnaire-9, respectively. Dyadic data were analyzed by the APIM approach. In this method, actor effect is the impact of a person's depression on his/her own QoL. Partner effect is the impact of a person's depression on his/her partner's QoL.Results from APIM revealed that both males and females' depression exuded an actor effect on their own QoL (β = - 0.589, p < 0.001; β = - 0.588, p < 0.001, respectively). Furthermore, males' depression exuded a significant partner effect on their wives' QoL (β = - 0.128, p = 0.030). Although the partner effect of females' depression on males' QoL was not statistically significant (β = - 0.108, P = 0.070), males whose wives had higher depression were more to indicate their own QoL was poorer. Based on equality constraint test, both actor and partner effects of depression on QoL were similar between males and females.The findings suggest that QoL in infertile patients was influenced by not only their own depression but also their spouses' depression; therefore, interventions to improve QoL should include both males and females.