Health care costs are an increasingly important study outcome. Endoscopic practice consumes a large proportion of gastroenterology-related health expenses. An economic comparison of several currently accepted endoscopic practices was performed, ranking them according their cost-effectiveness, as viewed from the payer perspective. The cost-effectiveness of four currently accepted standard endoscopic practices was examined: small bowel biopsy to assess for celiac sprue, colonoscopic biopsy to assess for microscopic colitis, surveillance of Barrett’s esophagus, and surveillance of chronic ulcerative colitis (CUC). Parameter estimates were obtained from the published literature. Charges were based on Medicare professional plus facility/technical fees. Performing colonoscopic biopsies for microscopic colitis in the setting of chronic nonbloody diarrhea was the most cost-effective practice ($2447/case detected), while small bowel biopsy for sprue in the setting of a patient with a first−degree relative with sprue ($3042/case detected) or with anemia ($2982/case detected) was also a cost−effective approach. Small bowel biopsy in the setting of diarrhea ($3900/case detected) was less cost-effective, while CUC surveillance ($14,119/detection of dysplasia) and performance of small bowel biopsy in an asymptomatic patient ($15,209/case detected) were clearly the least economical. As efforts are made to reduce the costs of health care, more attention will be focused on the cost-effectiveness of routine endoscopic practices. Although, our findings put endoscopic practices into economic perspective, future perspective, future prospective trials are required to confirm the validity of these findings.