Polycystic ovary syndrome (PCOS) is associated with poor quality of life (QoL) and high levels of depression. Existing research is confounded by small sample sizes and inconsistent use of control groups. METHODS: Depression and QoL were assessed in women with PCOS and healthy controls (n = 1359). The polycystic ovary syndrome health-related QoL questionnaire (PCOSQ) was modified to include an acne subscale. RESULTS: Seventy-one percentage of women with PCOS who were taking anti-androgen (AA) medication and 67% not taking AA medication were classified as depressed. Women with PCOS had lower QoL on all seven factors of the modified PCOSQ (emotional disturbance, weight, infertility, acne, menstrual symptoms, menstrual predictability and hirsutism). Weight was the largest contributor to poor QoL for women taking and not taking AA medication. Women taking AA medication, independent of diagnosis, generally had better QoL than women not taking them. CONCLUSIONS: This large study refines our understanding of depression and QoL in PCOS and demonstrates the need to regularly review the psychological health of women with PCOS.