Orangutans are noteworthy among great apes in their predilection for chronic, insidious, and ultimately fatal respiratory disease. Termed Orangutan Respiratory Disease Syndrome (ORDS), this cystic fibrosis–like disease is characterized by comorbid conditions of sinusitis, mastoiditis, airsacculitis, bronchiectasis, and recurrent pneumonia. The aim of this retrospective study was to determine the sensitivity of clinical signs in the diagnosis of ORDS in Bornean orangutans (Pongo pygmaeus) compared with the gold standard for diagnosis via computed tomography (CT). We retrospectively compared observed clinical signs with CT imaging in a population of clinically affected animals at an orangutan rescue center in southeastern Borneo. From August 2017 to 2019, this center housed 21 ORDS-affected animals, all of which underwent CT imaging to delineate which areas of the respiratory tract were affected. We reviewed clinical signs recorded in medical records and keeper observation notes for each individual for the period of 2 years prior to the date of the CT scan. A chi-square test of association was used to assess whether the observed clinical signs could predict the results of CT imaging. Results show that clinical signs may not be sensitive indicators in predicting respiratory disease identified by CT imaging. Based on the results of this study, clinical signs appear to be very poor predictors of underlying respiratory pathology in orangutans, based on high P-values, low sensitivity, and low specificity. This result is observed even with clinical signs data gathered over a full 24-mo period prior to CT scan performance. The findings of this study suggest the need for advanced imaging to properly diagnose and manage the most common health issue of captive orangutans.