OBJECTIVE: To identify systematic errors in surgeons' estimations of the importance of diagnostic variables in the decision to explore patients with suspected appendicitis. DESIGN: Prospective case series. SETTING: Two emergency departments, Sweden. PATIENTS: 496 patients with suspected appendicitis on admission, of whom 194 had a correct operation for appendicitis and 59 had a negative exploration. MAIN OUTCOME MEASURES: Predictors of a negative exploration expressed as the odds ratio (OR) for negative exploration. Variables influence on the decision to operate, expressed as the OR for operation, compared with the true diagnostic importance, expressed as the OR for appendicitis. RESULTS: Predictors of negative explorations were high ratings in variables describing pain and tenderness (patient's perceived pain, abdominal tenderness, rebound tenderness, guarding or rectal tenderness), weak or absent inflammatory response, female sex, long duration of symptoms and absence of vomiting, with OR of 1.8-3.0. Pain and tenderness had too strong an influence on the decision to operate whereas the lack of an inflammatory response, no vomiting, and long duration of symptoms were not given enough attention. There was no sex difference in the proportion of patients with non-surgical abdominal pain (NSAP) who were operated on, but NSAP was more common and appendicitis less common among women, leading to a larger proportion of negative appendicectomies among women. CONCLUSION: Negative explorations in patients with suspected appendicitis are related to systematic errors in the clinical diagnosis with too strong an emphasis on pain and tenderness, and too little attention paid to duration of symptoms and objective signs of inflammation. Rectal tenderness is not a sign of appendicitis. The risk of diagnostic errors is similar in men and women.