Aims and Objectives: The study was designed with the broad objective of determining the safety profile of artemisinin-based combination therapies amongst Nigerian population. Patients and Methods: This was a cohort event monitoring (CEM) programme involving monitoring adverse events (AEs) in malaria patients treated with either artemether-lumefantrine (AL) or artesunate-amodiaquine (AA) in healthcare facilities in Nigeria. The study involved continuous enrolment of patients with malaria and treated with either AL or AA at the various sites until a total cohort of 600 patients were enrolled at each site. Patients were monitored from the onset of therapy, and on days 3 and 7 from the first day of treatment to identify AEs that may occur. Results: A total of 6102 AEs were recorded in 10,259 patients monitored during the programme. Of 4896 patients who received AA, 4233 (86.5%) patients reported at least one AE while 1869 (34.8%) AEs out of 5363 patients who received AL were reported (P = 0.010). The predominant incidence of each specific AE reported in each group among the patients who received AA and AL includes body weakness 30.8%/7.5%, dizziness 10.3%/3.9%, restlessness 5.02/1.12%, vomiting 3.5/1.03% and drowsiness 3.1/1.5% for AA and AL, respectively. There were more AEs among patients with co-morbid conditions and patients in the younger age groups (9-<15 years), P = 0.000. Conclusions: Various types of AEs were seen and documented during the CEM programme. The findings suggested that the AA/AL monitored during this programme was generally safe and remarkably well tolerated among the Nigerian populations.