To identify enteropathogens for vaccine development, we implemented clinic-based surveillance for severe pediatric diarrhea in Egypt's Nile River Delta. Over 2 years, a physician clinically evaluated and obtained stool samples for microbiology from patients with diarrhea and less than 6 years of age. In the first (N = 714) and second clinic (N = 561), respectively, 36% (N = 254) and 46% (N = 260) of children were infected with rotavirus, enterotoxigenic Escherichia coli (ETEC), Campylobacter, or Shigella. When excluding mixed rotavirus-bacterial infections, for the first and second clinic, 23% and 10% had rotavirus-associated diarrhea, and 14% and 17% had ETEC-associated diarrhea, respectively. Campylobacter-associated diarrhea was 1% and 3%, and Shigella-associated diarrhea was 2% and 1%, respectively, for the two clinics. Rotavirus-associated diarrhea peaked in late summer to early winter, while bacterial agents were prevalent during summer. Rotavirus-associated cases presented with dehydration, vomiting, and were often hospitalized. Children with Shigella- or Campylobacter-associated diarrhea reported as watery diarrhea and rarely dysentery. ETEC did not have any clinically distinct characteristics. For vaccine development and/or deployment, our study suggests that rotavirus is of principle concern, followed by ETEC, Shigella, and Campylobacter.