The WHO estimated the annual rotavirus-related mortality among children below 5 years old in Egypt in 2004 to be 30 deaths per 100 000, or out of an estimated 2616 deaths, 3.9% were because of rotavirus infection. The aim of this article was to study the epidemiology and circulating genotypes of rotaviruses in Cairo from 2011 to 2012. A total of 197 stool samples were collected from 130 inpatient children at the Cairo University Children Hospital and 67 outpatient children at the Al-Saff Children Clinic. The collected stool samples were then screened for rotavirus using enzyme immunoassay, followed by a screening for G-type and P-type using RT-PCR, and confirmation by sequence analysis. Rotavirus was detected in 39.1% (77/197) of the children, with a higher rate in inpatients (43.9%, 57/130) than in outpatients (29.9%, 20/67). There was an increase of rotavirus infection in the winter season. The majority of rotavirus cases (85.7%) occurred during the first year of life. The predominant genotypes identified during this study were G3P[8] (37.7%) and G1P[8] (19.5%), but uncommon genotypes G1P[6] (3.9%), G9P[6] (1.3%), G8P[14] (1.3%), and G12P[6] (2.6%) were also detected. The change in genotype distribution, compared with previous studies, along with the high burden of rotavirus-associated diarrhea among Egyptian children below 2 years old, emphasizes the importance of continuing strain surveillance and the need of developing and introducing rotavirus vaccine in Egypt.