The clinical benefit of a diagnostic score for acute appendicitis was tested in a prospective interventional multicenter study on patients with abdominal pain. The study was performed in two consecutive phases: standard diagnostic work-up with no additional diagnostic support (870 patients) and additional diagnostic support with a score (614 patients). The two groups were comparable with respect to signs, symptoms and investigations related to acute appendicitis. Diagnostic performance of the final examiner decreased with the score: specificity from 86% to 78%, positive predictive value from 67% to 50% and accuracy from 88% to 81%. There were no differences in the perforated appendix, negative appendectomy and complication rate, however, the delayed appendectomy rate (2% versus 8%) and the delayed discharge rate (11% versus 22%) were significantly lower with diagnostic support by the score. In summary, the score cannot be recommended as a standard diagnostic tool for diagnostic decision making in acute appendicitis.