OBJECTIVE To assess the in vivo efficacy and adverse effects of Artemether-lumefantrine combination in acute uncomplicated falciparum malaria. METHODS A prospective, observational study was conducted at Department of Medicine and Pathology, Pakistan Medical level II hospital, Tubmanburg and Harper from March 2009 to September 2009. One hundred subjects with positive Plasmodium falciparum rings on malaria slide fulfilled the selection criteria and were included in the study. Mean, minimum and maximum values along with standard deviation of age, malarial parasite index, fever clearance time and parasite clearance time were calculated. A 28 day parasitological cure rate was determined. Frequency of various adverse events observed during this study were also noted. RESULTS Of 100 subjects, 70 wereAfricans while remaining were Asians. Mean fever clearance time in Africans and Asians were 18.9 +/- 11.5 and 27.9 +/- 14.3 hours respectively. The mean parasite clearance time was almost similar in both races ranging from 28 to 31 hours. A 28 day parasitological cure rate was found to be 100%. About 10% of the subjects developed mild to moderate side effects including headache, vomiting, loss of sleep, vertigo and diarrhoea. There was no mortality during the study. CONCLUSIONS Artemether Lumefantrine combination therapy may be used safely and effectively in the management of acute uncomplicated falciparum malaria.