To investigate the impact of the number of previous infertility treatment failures on anxiety and depression.In a cross-sectional study, individuals (men and women, but not couples) aged at least 18 years who had a history of infertility and could read and write in Persian were enrolled at the Royan Institute, Tehran, Iran, between November 1, 2013, and February 28, 2014. Participants provided demographic and infertility information and completed the Persian version of the Hospital Anxiety and Depression Scale (HADS).Overall, 330 patients (122 men, 208 women) were included. Mean scores on the HADS anxiety and depression subscales (HADS-A and HADS-D) were 8.40±4.51 and 5.95±3.54, respectively. In multiple regression analysis, mean HADS-A scores were significantly higher for patients with one treatment failure (9.57±4.58) than for those without a history of treatment (7.79±4.13; P=0.003). HADS-D scores were significantly higher for patients with two failures (6.92±3.69) than for those with no previous treatment (5.59±3.79; P=0.019).Patients with infertility have increased depression and anxiety after infertility treatment failure. Counseling or treatment for these potential psychological effects should be considered after infertility treatment failure.