Background: Diarrhea is one of the major causes of morbidity and mortality among children in the developing countries. Each year 1.6 million children under 5 years old die as a result of diarrheal diseases. Based on the literature, the number of children death due to diarrheal diseases each year might be 2.5 million, especially in developing countries. The main reasons of diarrhea are unsafe water supply, inadequate sanitation and hygiene. In Armenia, about 7% of infant deaths are associated with diarrheal diseases. Based on data from the Armenian Demographic Health Survey 2005 (ADHS 2005), 17% of children under-five years of age had diarrhea in the two weeks preceding the survey. Based on the ADHS 2005, from 2000 to 2005 this percent more than doubled from 8% to 17%. Methods: An analytical cross-sectional study design was used to assess the level of maternal knowledge and practices related to the management of childhood diarrhea and its association with the prevalence and duration of childhood diarrhea in Yerevan. The study population was mothers who have children 0-2 years-old. From two polyclinics, which were chosen by convenience sampling, mothers were chosen using systematic random sampling strategy. Sample size was estimated to be 276. Data collection was done by interviewer-administered telephone-based questionnaire. SPSS and STATA statistical packages were used for data entry and analysis. Results: The result of the simple linear regression (SLR) showed that the reported mean duration of childhood diarrhea was higher among the children who were less than 9 months of age, whose mothers were less than 30 years-of-age, whose mothers sought health care from a physician, provided them anti-motility medicines and gave them homemade medicine. An association was found between mean knowledge score of mothers and maternal age- on the average, for each one-year increase of maternal age there was an increase in maternal knowledge score on 0.1 units. Recommendation: Based on the finding of this research, programs to increase mothers’ knowledge about childhood diarrheal management could include an educational role for more experienced older mothers with younger mothers in a management of this disease. Respected older mothers who were shown to be more effective in the management of childhood diarrheal diseases than younger mothers could be trained to teach and provide examples for the less experienced younger mothers