At the end of the 90s in Peru, after determining the resistance to antimalarial drugs, a change in antimalarial treatment schemes was decided; this change included the combined therapy for P. falciparum, mefloquine/artesunate in the Amazon region, and sulfadoxine pyrimethamine/artesunate in the North coast. After two decades, and aimed at assessing the impact of these schemes on the malaria endemic, a review was conducted of malaria reports in three departments accounting for more than 70% of cases reported in the country. The major impact of the sulfadoxine-pyrimethamine/ artesunate scheme in the North coast was evident since it reduced the number of cases of P. falciparum to virtually zero four years after implementation of the combined therapy. The single dose and the ability to limit the development of sporozoites were crucial in order to achieve this goal. The mefloquine/artesunate scheme had the limitation of ensuring supervised treatment in the health service facilities and the need for three doses. It is important to select an effective and easy-to-administer scheme when choosing the first line of treatment for malaria. This experience is significant for the malaria eradication goals in Peru.