Objective: To validate published diagnostic models for their ability to safely reduce unnecessary endoscopy referrals in primary care patients suspected of significant colorectal disease. Study Design and Setting: Following a systematic literature search, we independently validated the identified diagnostic models in a cross-sectional study of 810 Dutch primary care patients with persistent lower abdominal complaints referred for endoscopy. We estimated diagnostic accuracy measures for colorectal cancer (N = 37) and significant colorectal disease (N = 141; including colorectal cancer, inftammatory bowel disease, diverticulitis, or >1-cm adenomas). Results: We evaluated 18 models-12 specific for colorectal cancer, of which most were able to safely rule out colorectal cancer: the best model (National Institute for Health and Care Excellence-1) prevented 59% of referrals (95% confidence interval [CI]: 56-63%), with 96% sensitivity (95% CI: 83-100%), 100% negative predictive value (NPV; 95% CI: 99-100%), and an area under the receiver operating characteristics curve (AUC) of 0.86 (95% CI: 0.80-0.92). The models performed less for significant colorectal disease: the best model (Brazer) prevented 23% of referrals (95% CI: 20-26%), with 95% sensitivity (95% CI: 90-98%), 96% NPV (95% CI: 92-98%), and an AUC of 0.73 (95% CI: 0.69-0.78). Conclusion: Most models safely excluded colorectal cancer in many primary care patients with lower gastrointestinal complaints referred for endoscopy. Models performed less well for significant colorectal disease. (C) 2016 Elsevier Inc. All rights reserved.