A definitive conclusion regarding the value of low-dose extended duration adjuvant interferon-alpha therapy in the treatment of malignant melanoma is only possible once data on health-related quality of life (HRQoL) and costs have been considered. This trial randomised 674 patients to interferon alpha-2a (3 megaunits three times per week for 2 years or until recurrence) or placebo. Health-related quality of life (QoL) was to be assessed up to 60 months using the European Organisation for Research and Treatment of Cancer (EORTC) QLQ-C30. Data for the economic analysis, including cost information and the EQ-5D were also collected. Patients in the observation (OBS) group had significantly better mean follow-up quality of on five dimensions of the EORTC QLQ-C30 functional scales: role functioning (P = 0.033), emotional functioning (P = 0.003), cognitive functioning (P = 0.001), social functioning (P = 0.003) and global health status (P = 0.001). Patients in the OBS group had significantly better mean follow-up symptom scores on seven dimensions of the EORTC QLQ-C30 V1 symptom scales. Economic data showed that costs were 3066 pounds higher in the interferon group and produces an incremental cost per quality-adjusted life year of 41,432 pounds at 5 years. The results show that interferon has significant effects on QoL and symptomatology and is unlikely to be cost-effective in this patient group in the UK.