OBJECTIVES: The METRIC trial demonstrated clinical benefits of trametinib vs. chemotherapy (dacarbazine or paclitaxel) in patients with BRAF V600+ advanced or metastatic melanoma overall, and in a subgroup receiving 1L treatment. We evaluated the cost-effectiveness of trametinib as a 1L treatment vs. approved treatments (dacarbazine and vemurafenib) in Canada from a societal perspective.  METHODS: A partitioned survival analysis model with 3 health states (pre-progression, post-progression, dead) estimated direct and indirect costs and quality-adjusted life-years (QALYs) for patients with BRAF V600+ advanced or metastatic melanoma receiving 1L treatment with trametinib, dacarbazine, or vemurafenib. Clinical inputs for trametinib and dacarbazine were from the METRIC trial (in the 1L chemotherapy group, 87%, 6% and 6% of patients received dacarbazine, paclitaxel, and no drug, respectively). Clinical inputs for vemurafenib were from an indirect treatment comparison of data from the METRIC and BRIM-3 studies. Resource utilization data were derived from physician survey results, drug costs from the manufacturers’ price and Quebéc medications lists, and other costs from published sources. Consistent with a prior evaluation of vemurafenib, a 5-year time horizon was used. Costs and QALYs were discounted at 5% annually.  RESULTS: QALYs gained with trametinib were 0.4160 vs. dacarbazine and 0.1241 vs. vemurafenib. Compared with dacarbazine, incremental costs for trametinib were $61,226, resulting in a cost of $147,177 per QALY gained. Compared to vemurafenib, trametinib yielded a cost savings of $26,553 and was therefore dominant (less costly, more effective). Probabilistic sensitivity analyses showed a 14% and 98% probability of trametinib being cost effective vs. dacarbazine and vemurafenib, respectively, based on a $100,000/QALY threshold.  CONCLUSIONS: In patients with BRAF V600+ advanced or metastatic melanoma, 1L treatment with trametinib may not be cost-effective vs. dacarbazine but may be cost-effective vs. vemurafenib. There is uncertainty in the vemurafenib comparison given the lack of head-to-head data.