Background. Artificial neural networks (ANN) have been used in the prediction of several medical conditions but have not been previously used to predict pneumonia. The authors used ANN to predict the presence or absence of pneumonia among patients presenting to the emergency department with acute respiratory complaints and compared the results with those obtained using logistic regression modeling. Methods. Feed-forward back-propagation ANN were trained on sociodemographic, symptom, sign, comorbidity, and radiographic outcome data among 1044 patients from the University of Illinois (the training cohort) and were applied to 116 patients from the University of Nebraska (the testing cohort). ANN trained using different strategies were compared to each other and to main-effects logistic regression. Calibration accuracy was measured as mean square error and discrimination accuracy as the area under a receiver operating characteristic (ROC) curve. Results. A 1 hidden-layer ANN trained using oversampling of pneumonia cases had an ROC area in the training cohort of 0.895, which was greater than the area of 0.840 for logistic regression ( P = 0.026). This ANN had an ROC area in the testing cohort of 0.872, not significantly different from its area in the training cohort ( P = 0.597). Operating at a threshold of 0.25, the ANN would have detected 94% to 95% of patients with pneumonia in the 2 cohorts while correctly excluding 39% to 50% of patients with other conditions. ANN trained using other strategies discriminated equally in the 2 cohorts but no better than did logistic regression. Conclusions. Among adults presenting with acute respiratory illness, ANN accurately discriminated patients with and without pneumonia and, under some circumstances, improved on the accuracy of logistic regression.