While results from a Plasmodium vivax dynamic model have shown the potential impact of quantitative glucose-6-phosphate dehydrogenase (G6PD) test-and-treat strategies using tafenoquine for radical cure on cases averted, the cost-effectiveness has not been previous explored using a transmission model framework. Here, we explore the impact on the overall cost-effectiveness in Brazil using a 10-year time horizon using four scenarios: 1) tafenoquine for adults only, 2) tafenoquine for children aged >6 months, 3) Scenario 1 with 90% primaquine adherence, 4) Scenario 1 with 30% primaquine adherence. In Scenarios 1 & 2, primaquine treatment adherence was 66.7%. The incremental cost-effectiveness ratios (ICERs) were estimated by dividing the incremental costs by the disability-adjusted life-years (DALYs) averted as compared to usual practice (primaquine without G6PD screening). Consistent with Brazilian guidelines, costs and DALYs were discounted by 5% in order to value time in the present over costs and benefits in the future. The ICERs were compared to a willingness to pay (WTP) threshold of US$16,700 for Brazil, which was set by Brazil’s Health Technology Assessment body (CONITEC). One-way and probabilistic sensitivity analyses were performed. We found that all four scenarios were very cost-effective (>99% likelihood) using this WTP threshold with Scenario 4 saving costs while averting DALYs. Scenarios 1-3 had ICERs ranging from US$233-1542. One-way sensitivity analyses showed that the results were most sensitive to the lifetime and number of quantitative G6PD machines needed, severity and mortality due to vivax. malaria, cost of G6PD test strips, and life expectancy. Our results provide strong evidence that tafenoquine prescribed after a quantitative G6PD test is highly likely to be cost-effective in Brazil.