Background  DAV‐interferon (IFN)‐β therapy is a combination chemotherapy of dacarbazine (DTIC), nimustine (ACNU) and vincristine (VCR) with local subcutaneous injection of IFN‐β that is widely employed as postoperative adjuvant chemotherapy to treat malignant melanoma in Japan. However, the efficacy of DAV‐IFN‐β therapy has not been confirmed by randomized controlled trials and the benefit of DAV‐IFN‐β therapy has not been established yet. This study evaluated the contribution of DAV‐IFN‐β therapy to improve survival of postoperative patients with cutaneous melanoma. Methods Patients with stage II or III cutaneous melanoma seen at Nagoya University Hospital from January 1998 to December 2009 were eligible for this study. Disease‐free survival rates and melanoma‐specific survival rates were evaluated. A propensity score was calculated to control for the effects of variables related to decisions regarding the application of DAV‐IFN‐β therapy. Results  Eighty‐two stage II and 60 stage III melanoma patients were included. In the post‐matched stage II patients (17 matched pairs), the mean (±SE) disease‐free survival rates were 39.9±13.7% for DAV‐IFN‐β therapy and 73.1±11.7% for non‐use (hazard ratio for recurrence, 2.06; 95% CI, 0.63–6.69; P = 0.23), and the melanoma‐specific survival rates were 66.2±20.0% for DAV‐IFN‐β therapy and 86.2±9.1% for non‐use (hazard ratio for death, 1.09; 95% CI, 0.17–6.82; P = 0.93). In the post‐matched stage III patients (nine matched pairs), the disease‐free survival rates were 29.6±16.4% for DAV‐IFN‐β therapy and 33.3±15.7% for non‐use (0.69; 95% CI, 0.22–2.17; P = 0.53), and the melanoma‐specific survival rates were 55.6±16.6% for DAV‐IFN‐β therapy and 44.4±16.6% for non‐use (0.67; 95% CI, 0.18–2.50; P = 0.55). Conclusions  DAV‐IFN‐β therapy brought no significant improvement in either disease‐free survival rates or melanoma‐specific survival rates of patients with stage II or III cutaneous melanoma. A randomized controlled trial would be required to further evaluate the efficacy of DAV‐IFN‐β therapy as an adjuvant chemotherapy.