Background: Dabrafenib is a potent inhibitor of mutated BRAF kinase in BRAF V600E/K mutation–positive metastatic melanoma (mut⁺ MM). This multicenter, single-arm phase 2 study assessed safety and clinical activity of dabrafenib in BRAF V600E/K mut⁺ MM. We previously reported the primary endpoint of investigator-assessed overall response rate in BRAF V600E mut⁺ MM patients and overall survival (OS; median follow-up 11.9 months). Here we report long term safety data and updated OS (median follow-up 13 months). Methods: 92 patients with histologically confirmed stage IV BRAF V600E/K mut⁺ MM received oral dabrafenib 150 mg twice daily until disease progression, death, or unacceptable adverse events (AEs). Secondary endpoints included safety and OS. AEs were summarized by duration of dabrafenib treatment. Results: 76 patients with BRAF V600E mut⁺ MM and 16 with BRAF V600K mut⁺ MM were enrolled from August 2010 to February 2011. As of December 2013, 11 patients (12%) had not experienced a progression event and 9 continued to receive dabrafenib. In the BRAF V600K group, median OS was 12.9 months (95% CI, 6.9-17.1); 4 patients (25%) were alive beyond 18.8 months (third quartile OS; 95% CI, 12.9-NR). In the BRAF V600E group, median OS was 13.1 months (95% CI, 10.4-21.9); 21 patients (28%) were alive beyond 30 months (third quartile OS, NR). The most common AEs in all patients were arthralgia (35%), hyperkeratosis (33%), and pyrexia (29%). Overall, 33 patients (36%) experienced a serious AE; 13 (14%) had cutaneous squamous cell carcinoma. New primary melanoma and other malignancies occurred in 2 patients (2%). For patients on dabrafenib > 24 months (n = 11), hyperkeratosis (64%), arthralgia (55%), and pyrexia (45%) were the most common AEs observed during treatment, and 2 patients (18%) experienced serious AEs during treatment. Conclusions: 25 patients were alive as of December 2013, and 9 of those patients were receiving treatment with dabrafenib. Median OS was > 1 year in patients with BRAF V600E/K mut⁺ MM treated with dabrafenib. The most common AEs in patients treated with dabrafenib > 24 months were the same as those in patients treated with dabrafenib < 24 months. Clinical trial information: NCT01153763.