ABSTRACT: Decades after the establishment of clear guidelines for management, mostly due to irrational approach, diarrhea is still a major concern in the developing world, including India. The scenario is even worse in urban slums owing to poor health-seeking and socio-environmental vulnerability. Determining the distribution of rational diarrhea management by practitioners and identification of its important predictors seemed urgent to minimize the potential for antibiotic resistance, diarrhea-related mortality and morbidity in these areas.Between May 2011 and January 2012, 264 consenting, randomly selected qualified and non-qualified practitioners (including pharmacists) were interviewed in the slums of Kolkata, a populous city in eastern India, regarding their characteristics, diarrhea-related knowledge (overall and in six separate domains: signs/symptoms, occurrence/spread, management, prevention/control, cholera and ORS), prescribed antibiotics, intravenous fluid (IVF) and laboratory investigations. Rationality was established based on standard textbooks.Among participants, 53.03% had no medical qualifications, 6.06% were attached to Governmental hospitals, 19.32% had best knowledge regarding diarrhea. While treating diarrhea, 7.20%, 17.80% and 20.08% respectively advised antibiotics, IVF and laboratory tests rationally. Logistic regression revealed that qualified and Governmental-sector practitioners managed diarrhea more rationally. Having best diarrhea-related knowledge regarding signs/symptoms (OR=5.49, p value=0.020), occurrence/spread (OR=3.26, p value=0.035) and overall (OR=6.82, p value=0.006) were associated with rational antibiotic prescription. Rational IVF administration was associated with best knowledge regarding diarrheal signs/symptoms (OR=3.00, p value=0.017), occurrence/spread (OR=3.57, p value=0.004), prevention/control (OR=4.89, p value=0.037), ORS (OR=2.55, p value=0.029) and overall (OR=4.57, p value<0.001). Best overall (OR=2.68, p value=0.020) and cholera-related knowledge (OR=2.34, p value=0.019) were associated with rational laboratory testing strategy.Diarrheal management practices were unsatisfactory in urban slums where practitioners' knowledge was a strong predictor for rational management. Interventions targeting non-qualified, independent practitioners to improve their diarrhea-related knowledge seemed to be required urgently to ensure efficient management of diarrhea in these endemic settings.