In the last few decades, increasing use of antibiotics has dramatically increased the incidence of antibiotic-associated diarrhea. An unopposed homing of Clostridium difficile in intensive care unit (ICU) and wards puts forward new challenges for physicians. Development of diarrhea during or just after hospital stay, especially in old patients, is a typical clinical presentation of C. difficile diarrhea. Cytotoxin assay from tissue culture is a gold standard diagnostic test but its poor availability, high cost, time bound results and rapid development of life-threatening complications made us to think of a screening test. Demonstration of pathognomonic summit lesions and pseudomembrane with colonoscopy or sigmoidoscopy is relatively inexpensive, easily available and diagnosis is prompt. Our experience in few patients with colonoscopy makes us recommend it as a screening test for all clinically suspected patients. It is refuted as first-line investigation because of good number of false negative results but demonstration of pathognomonic lesions even in few patients saves the life with minimal expenditure and least time wastage before initiation of definitive treatment.