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, inflammatory bowel disease, diverticulitis, or >1cm 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 (NICE-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