Background: Several modifications of the 13C‐urea breath test have been published. For reasons of cost efficiency and practicability, the urea dose and measurement duration should be reduced while still maintaining excellent diagnostic accuracy. Aims: To establish a validated simple protocol for the urea breath test with 50 mg 13C‐urea and to compare this protocol with the conventional urea breath test with 100 mg 13C‐urea. Methods: Conventional urea breath test with 100 mg 13C‐urea was performed on 152 dyspeptic patients. Full‐cream cow's milk was used as the test meal. Breath tests were repeated using 50 mg 13C‐urea and the breath samples were collected at baseline and at 10 (protocol t10), 15 (protocol t15) and 30 min (protocol t30). Helicobacter pylori status was assessed by rapid urease test, histology and conventional urea breath test with 100 mg 13C‐urea. Results: With protocol t15, the best combination of sensitivity (99.1%), specificity (97.3%) and accuracy (98.7%) was obtained with a cut‐off of 2.5‰. There was an extremely high correlation coefficient between the three protocols and conventional 13C‐urea breath test (all P < 0.001). Conclusions: A urea breath test with 50 mg 13C‐urea using a simple test meal and a 15‐min sampling interval with a low cut‐off seems to be cost‐effective and convenient. In a well‐standardized laboratory, this modification is not associated with any loss of diagnostic accuracy.

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