Abstract Background Upper gastrointestinal (UGI) series is the standard imaging tool for diagnosis of structural and functional abnormalities affecting the esophagus, stomach, and proximal small bowel. The aim of this study was to delineate the clinical indications for UGI series in children that are associated with the presence of significant radiological abnormalities aiming for more standardized care for those patients. Results UGI series of 118 patients was analyzed with calculation of clinical score. Vomiting was the most frequent primary complaint (63.6%), followed by dysphagia and recurrent chest infection. Forty-nine patients had positive upper GI findings (42%). The most detected abnormality was related to the stomach and duodenum (21.4%). Variable degrees of idiopathic gastroesophageal reflux were detected in 16 patients (13.6%). Patients with clinical score 2 or more had significantly more prevalence of abnormal findings (p = .001). Vomiting (especially when bilious), underweight, aspiration, and recurrent chest infection were strong predictors of abnormal findings on upper GI series (p = 0.007, 0.001, 0.009, and 0.001, respectively) and increased the diagnostic yield of upper GI series for detection of abnormalities by 3.48, 9.6, 4, and 4.12 times, respectively. Conclusion Diagnostic yield of UGI series was relatively higher in patients having two or more symptoms (clinical score 2 or more) and in children with bilious vomiting, aspiration and underweight, or repeated chest infection.