Abstract: Malaria is still a major public health concern which leads to over 400,000 deaths globally especially in the pediatric population under five years. In Kenya, artemether –lumefantrine is the first-line drug recommended for the treatment of uncomplicated falciparum malaria. Although it has shown good efficacy and high cure rates, drug tolerability, patient non-compliance, administration with fat-rich foods for optimal absorption, and the emerging threat of artemisinin resistance are its major throwbacks. Thus, the need for improving the existing artemisinin-based therapies with novel partner drugs like pyronaridine to overcome these limitations. This study was a component of phase III single- blind randomized non-inferiority study in Mbita, Kenya that included patients of ≤ 12 years with a bodyweight of ≥ 5 kg and microscopically confirmed Plasmodium falciparum malaria. Eligible children were randomized (1:1) to receive either pyronaridine-artesunate or artemether-lumefantrine orally for three days according to their bodyweights and followed for 42 days for therapeutic responses. Of 155 patients, 81 received pyronaridine-artesunate while 74 received artemether-lumefantrine. A higher proportion of aparasitemic patients in pyronaridine-artesunate cohort was registered compared with artemether-lumefantrine (96.3% versus 95.8%) on day 3. Time to parasite clearance significantly differed between the treatment arms (p<0.05). Despite the significant difference in the proportions of parasitemic patients on days 28 and 42 (p< 0.05), there was no significant differences in day 28 and 42 ACPR without PCR corrections in both study comparators (p>0.05). This present study showed that pyronaridine-artesunate was efficacious as artemether-lumefantrine in the treatment of uncomplicated falciparum malaria.