Diarrheal disease is a leading cause of death among young children worldwide. As rates of acute diarrhea (AD; 1-6 days duration) have decreased, persistent diarrhea (PD; > 14 days duration) accounts for a greater proportion of the diarrheal disease burden. We describe factors associated with the duration of moderate-to-severe diarrhea in Kenyan children < 5 years old enrolled in the Global Enteric Multicenter Study. We found 587 (58%) children experienced AD, 360 (35%) had prolonged acute diarrhea (ProAD; 7-13 days duration), and 73 (7%) had PD. We constructed a Cox proportional hazards model to identify factors associated with diarrheal duration. Risk factors independently associated with longer diarrheal duration included infection with Cryptosporidium (hazard ratio [HR]: 0.868, P = 0.035), using an unimproved drinking water source (HR: 0.87, P = 0.035), and being stunted at enrollment (HR: 0.026, P < 0.0001). Diarrheal illness of extended duration appears to be multifactorial; given its association with adverse health and development outcomes, effective strategies should be implemented to reduce the duration and severity of diarrheal illness. Effective treatments for Cryptosporidium should be identified, interventions to improve drinking water are imperative, and nutrition should be improved through exclusive breastfeeding in infants ≤ 6 months and appropriate continued feeding practices for ill children.