There is lack of information in the medical literature on clinically diagnosed Down syndrome children presenting with diarrhea. Our aim was to describe our experience with Down syndrome patients admitted with diarrhea by evaluating the factors associated with Down syndrome presenting with diarrheal illness. In this retrospective chart analysis, we enrolled all the diarrheal children aged 0–59 months admitted to the Dhaka Hospital of the International Centre for Diarrheal Disease Research, Bangladesh (icddr, b), from March 2011 to February 2013. Down syndrome children with diarrhea constituted cases and randomly selected threefold diarrheal children without Down syndrome constituted controls. Among 8422 enrolled children 32 and 96 were the cases and the controls, respectively. Median age (months) of the cases and the controls was comparable (7.6 (4.0, 15.0) versus 9.0 (5.0, 16.8); p=0.496). The cases more often presented with severe acute malnutrition, developmental delay, congenital heart disease, hypothyroidism, sepsis, hypocalcemia, developed hospital acquired infection (HAI) during hospitalization, and required prolonged stay at hospital compared to the controls (for all p<0.05). Thus, diarrheal children with clinically diagnosed Down syndrome should be investigated for these simple clinical parameters for their prompt management that may prevent HAI and prolonged hospital stay.