Study design: Severe falciparum malaria in children was studied as part of the characterization of the Kassena-Nankana District Ghana for future malaria vaccine trials. Children aged 6 - 59 months with diagnosis suggestive of acute disease were characterized using the standard WHO definition for severe malaria. Results: Of the total children screened, 45.2% (868/ 1921) satisfied the criteria for severe malaria. Estimated incidence of severe malaria was 3.4% ( range: 0.4 - 8.3%) cases per year. The disease incidence was seasonal: 560 cases per year, of which 70.4% occurred during the wet season ( June-October). The main manifestations were severe anaemia ( 36.5%); prolonged or multiple convulsions ( 21.6%); respiratory distress ( 24.4%) and cerebral malaria ( 5.4%). Others were hyperpyrexia ( 11.1%); hyperparasitaemia ( 18.5%); hyperlactaemia ( 33.4%); and hypoglycaemia ( 3.2%). The frequency of severe anaemia was 39.8% in children of six to 24 months of age and 25.9% in children of 25 - 60 months of age. More children ( 8.7%) in the 25 - 60 months age group had cerebral malaria compared with 4.4% in the 6 - 24 months age group. The overall case fatality ratio was 3.5%. Cerebral malaria and hyperlactataemia were the significant risk factors associated with death. Severe anaemia, though a major presentation, was not significantly associated with risk of death. Conclusion: Severe malaria is a frequent and seasonal childhood disease in northern Ghana and maybe an adequate endpoint for future malaria vaccine trials.