Artemether-lumefantrine (AL) is the first-line treatment for uncomplicated Plasmodium falciparum infection in Colombia. To assess AL efficacy for uncomplicated falciparum malaria in Quibdo, Choco, Colombia, we conducted a 28-day therapeutic efficacy study (TES) following the WHO guidelines. From July 2018 to February 2019, febrile patients aged 5-65 years with microscopy-confirmed P. falciparum mono-infection and asexual parasite density of 250-100,000 parasites/µL were enrolled and treated with a supervised 3-day course of AL. The primary endpoint was adequate clinical and parasitological response (ACPR) on day 28. We attempted to use polymerase chain reaction (PCR) genotyping to differentiate reinfection and recrudescence, and conducted genetic testing for antimalarial resistance-associated genes. Eighty-eight patients consented and were enrolled; four were lost to follow-up or missed treatment doses. Therefore, 84 (95.5%) participants reached a valid endpoint: treatment failure or ACPR. No patient remained microscopy positive for malaria on day 3, evidence of delayed parasite clearance and artemisinin resistance. One patient had recurrent infection (12 parasites/µL) on day 28. Uncorrected ACPR rate was 98.8% (83/84) (95% CI: 93.5-100%). The recurrent infection sample did not amplify during molecular testing, giving a PCR-corrected ACPR of 100% (83/83) (95% CI: 95.7-100%). No P. falciparum kelch 13 polymorphisms associated with artemisinin resistance were identified. Our results support high AL efficacy for falciparum malaria in Choco. Because of the time required to conduct TESs in low-endemic settings, it is important to consider complementary alternatives to monitor antimalarial efficacy and resistance.