Human rotavirus infection was studied over a 13-month period (January 2004 to January 2005) in children <5 years of age admitted with severe diarrhea at the Korle-Bu Teaching Hospital in Accra, Ghana. During this period, 206 hospitalizations for diarrhea were recorded, with 34.0% (70/206) being positive for rotavirus infection. Infection occurred throughout the year, with peak rotavirus infection occurring during the month of March. Hospitalization associated with rotaviruses was most common in the 6–8 month age group. The case fatality rate of rotavirus infection was 2.9% (2/70) and occurred in children <12 months of age. Four rotavirus VP7 genotypes (G1, G2, G3, and G9) were detected. The predominant genotypes were G2 (22.9%), G1 (17.1%), G9 (17.1%) and G3 (12.9%). Mixed G types were also detected. The predominant VP4 genotypes (P types) were P[6] (38.6%), P[8] (21.4%), P[4] (4.3%) and P[9] (1.4%). The predominant rotavirus strains infecting children in Accra were G9P[6] (10.0%) and G1P[8] (8.6%). Strains with unusual genotypes such as G2P[8] and G(2/3)P[6] were also detected.