BACKGROUND: Patients with thick (Breslow>4 mm) primary melanoma and/or regional nodal metastasis have a high risk of tumor recurrence. High-dose adjuvant interferon (IFN) alfa-2b offers/=50% risk of recurrence/disease-related mortality and offered IFN. Telephone surveys delineated reasons behind patients' decisions to accept IFN. RESULTS: Acceptors, 60 of 135 (45%), decided to take IFN alfa-2b whereas 75 of 135 (55%) declined. Being female (OR, 2.4; 95% CI, 1.17-5.03; p=.017) and positive SLN status (OR, 2.2; 95% CI, 1.01-4.97; p=.048) were strongly associated with patients who chose IFN. Acceptors of IFN were younger, more influenced by physicians, and less affected by depression and side effect profile (p<.05 for all). Decliners were more concerned by strained relationships with family and social life (p<.05). CONCLUSIONS: Gender and positive SLN were predictive of high-risk melanoma patients' acceptance of IFN treatment. Physician insight into melanoma patients' therapeutic decision-making process can guide patients through this difficult disease.