Abstract Background and study aims Since the introduction of open-access esophago-gastroduodenoscopy (OAE) there is an increase in the total number of performed OAEs whilst the frequency of clinical relevant findings has decreased. The aim of this study was to assess the appropriate use and the diagnostic yield of OAE in the Netherlands and to determine which patient variables are able to predict a malignant finding. Patients and methods A retrospective chart review of all referrals for diagnostic OAE between October 2012 and October 2016 at the Northwest Clinics was performed. The indications were recorded from the referral letter and were classified as “appropriate” or “inappropriate” according to the NHG guideline. Logistic regression was used to detect significant predictive variables for a malignancy. Results A total of 2006 patients were included, of whom 59.6 % had an ‘appropriate’ referral indication. The diagnostic yield of finding a clinical relevant finding was significantly higher for OAEs with an “appropriate” referral indication. Independent risk factors for malignancy were alarm symptoms, age and male gender with a combined AUC of 0.868. Conclusions Only 3.8 % of the malignancies would be missed by strict adherence to the guideline. This indicates that the open-access system in the Netherlands works well. Further improvement of the system can be achieved by only accepting appropriate indications for OAE and by treating patients under the age of 40 without OAE. We showed that a risk-prediction model based on the variables age, alarm symptoms and male gender is a good predictor of malignant finding.