Background: Pembrolizumab demonstrated superior PFS over chemotherapy for ipilimumab-refractory melanoma (KEYNOTE-002) and superior OS and PFS over ipilimumab for advanced melanoma (KEYNOTE-006). Here we present 3-year OS data for all patients with melanoma enrolled in the phase 1b KEYNOTE-001 study (NCT01295827). Methods: Patients enrolled in ipilimumab-naive and ipilimumab-treated cohorts received pembrolizumab 2 or 10 mg/kg Q3W or 10 mg/kg Q2W. Response was assessed by RECIST v1.1 every 12 weeks. OS was estimated using the Kaplan–Meier method. Results: Of the 655 patients enrolled, 24% had BRAFV600 mutation, 78% had stage M1c disease, 38% had elevated lactate dehydrogenase, 75% had ≥1 prior therapy, and 52% had prior ipilimumab. As of the September 18, 2015 data cut off date, median follow-up was 32 months (range 24–46) and 358 (55%) patients had died. The 36-month OS rate was 40% and median OS was 23.8 months (95% CI, 20.2–29.0), with similar results for each dose (Table). Note that 36-month OS rates were 41% in both ipilimumabtreated and ipilimumab-naive patients and 45% in treatment-naive patients (Table). Examination of the OS curve suggests a long-term OS benefit for a fraction of patients treated with pembrolizumab. Additional data, including PFS, ORR, duration of response and safety, will be available for presentation. Conclusions: Pembrolizumab provides long-term survival benefit in patients with ipilimumab-naive and ipilimumab-treated advanced melanoma, with ~40% of patients alive at 3 years. These data support the use of pembrolizumab in patients with advanced melanoma regardless of prior treatment.