Upper endoscopy (esophagogastroduodenoscopy or EGD) is an important diagnostic tool for many gastrointestinal symptoms. In recent years, the number of EGDs has increased dramatically. Unfortunately, the rate of negative (normal) EGD in children is high, approximating 50% of all procedures. To decrease the cost of EGD procedures, it is important to assess which clinical symptom would detect positive findings. This information may also be valuable in improving the referral practices of the primary care physicians for EGD. In a retrospective study, we investigated the pathological yield of the first EGD in children referred for various symptoms. Abdominal pain was the most common referral symptom and the best predictor of positive EGD, reaching an accuracy level of 79.9%. All other investigated symptoms had less than 50% accuracy. We concluded that most gastrointestinal symptoms in children have a poor predictive value for positive EGD. A cost–benefit analysis of EGD in children is needed.