Objectives The objectives of this study were to determine the safety of the use of nonfixed-dose combination of artesunate (AS) and amodiaquine (AQ) in the treatment of uncomplicated falciparum malaria in pregnancy. In this regard, the focus was on the possible effects of the combination on biochemical and haematological parameters as well as other adverse drug reactions associated with the use of the drugs. Methods Ninety subjects were recruited from pregnant women on antenatal care visit to a busy hospital in Esan West Local Government Area, Edo State Nigeria. Fifty met the criteria for the diagnosis of uncomplicated malaria. They were placed on treatment with standard doses of AS 4 mg/kg and AQ 10 mg/kg daily for 3 days. Forty apparently healthy pregnant women and 30 nonpregnant women were used as control. Patients on AS + AQ combination were monitored closely for 28 days. Key findings There was a significant reduction in high-density lipoprotein cholesterol-C: 24.60 AE 1.20 mg/dl) in the test group (P < 0.05) when compared with pregnant control (27.57 AE 0.89 mg/dl) and a nonsignificant reduction (P > 0.05) in low-density lipoprotein cholesterol-C: 83.55 AE 6.10 mg/dl) levels compared with control (87.82 AE 4.88 mg/dl). Additionally, there was a nonsignificant elevation (P > 0.05) of conjugated bilirubin in the test group (0.48 AE 0.06 mg/dl) when compared with pregnant control (0.40 AE 0.04 mg/dl). Changes in haemoglobin concentration (10.45 AE 0.23 g/dl) and packed cell volume (31.37 AE 0.70%) in patients treated with AS + AQ combination were not significant compared with pregnant control (10.18 AE 0.27 g/dl and 31.17 AE 0.55% respectively). Alkaline phosphatase (120.27 AE 7.81 IU/l) was not significantly elevated (P > 0.05) in patients treated with AS + AQ combination compared with pregnant control (117.81 AE 10.61 IU/l). Conclusion We conclude that the use of this combination is safe and well tolerated in pregnant women with uncomplicated falciparum malaria.