Background: CLBS20 is a patient-specific therapeutic vaccine consisting of autologous dendritic cells loaded with antigens from irradiated cells from an autologous tumor cell line. It potentially presents the entire repertoire of unique antigens resulting from nonsynonymous mutations in a patient’s self-renewing melanoma cells. In previously reported single arm and randomized phase 2 trials, CLBS was associated with a 72% 2-year overall survival (OS). In the randomized trial median OS for CLBS20-treated patients was more than twice that for a vaccine consisting of irradiated autologous tumor cells. Mild local injection site reactions was the most common toxicity. Methods: During 2001 to 2011 72 patients with stage 4 or recurrent stage 3 melanoma were treated with CLBS20 (Clinicaltrials.gov NCT00948480 & NCT00436930). Each had a metastatic melanoma lesion surgically resected, from which a tumor cell line was established, cells from which were incubated with autologous dendritic cells to produce the vaccine that was injected s.c. in 500 micrograms sargramostim (GM-CSF) weekly x 3 weeks and monthly x 5 months (mos). This report summarizes long-term survival data for all CLBS20-treated patients from date of first injection. Results: There were 45 men and 27 women. Median age is 52 years (17 to 83). Tumor sources were 37-lymph node, 15-soft tissue, 20-viscera. Prior therapies included 72-surgery, 41-chemotherapy, 33-Interleukin-2, 30-interferon alpha, 24-GM-CSF, 19-radiation therapy (RT), and 15-RT for brain metastases. All 33 surviving patients were followed 5 years; none were lost to follow up. Median OS is 45.6 mos; 5-year OS is 46%. Median progression free survival (PFS) is 4.4 mos, 5-year PFS is 19%. The 20 patients with recurrent stage 3, have a 70% 5-year OS, median PFS 19.8 mos, and 35% 5-year PFS. For the 52 patients with stage 4, median OS is 41.0 mos, 5-year OS is 36%, and median PFS is 3.8 mos. One patient with refractory progressive measurable disease experienced a delayed complete response that was ongoing at 5 years. Conclusions: CLBS20 is associated with encouraging 5-year overall survival. Because of its unique mechanism of action and absence of toxicity, it should be evaluated further in similar patients. Clinical trial information: NCT00948480Clinical trial information: NCT00436930