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The role of chest radiography to diagnose active tuberculosis in symptomatic patients who have a negative Xpert MTB/RIF (Xpert) test result is unclear. This study aimed to assess the performance of chest radiography and the value of chest radiography findings for a prediction tool to identify cases of active pulmonary tuberculosis among symptomatic, Xpert-negative hospitalised patients.  Xpert-negative patients hospitalised between January and July 2019 at Jimma University Medical Center in Ethiopia were assessed by mycobacterial culture and chest radiography. Chest radiography was interpreted by a clinician for clinical decision making and by a radiologist for research purposes. Using bacteriological confirmation as the reference standard, the performance of chest radiography to diagnose active tuberculosis was assessed by the area under the receiver operating characteristic curve (AUC); predictors of active tuberculosis were identified using bivariate and multivariate logistic regression analyses.  Of 247 Xpert-negative patients, 38% and 40% were classified as suggestive of tuberculosis by clinician and radiologist, respectively. Of the 39 (15.8%) bacteriologically confirmed cases, 69% and 79% were classified as having chest radiography findings suggestive of tuberculosis by clinician or radiologist, respectively. While there was a strong association between bacteriologically confirmed tuberculosis and chest radiography classified by clinician as suggestive of tuberculosis (adjusted OR 2.7, 95% CI 1.2–6.6), chest radiography with signs typical of tuberculosis (adjusted OR 5.3, 95% CI 2.1–14.4) or compatible with tuberculosis (adjusted OR 5.1, 95% CI 1.3–20.0), the positive predictive value of the chest radiography was low (27% and 34% for classification by clinician and radiologist, respectively). The addition of chest radiography findings by clinician or radiologist to clinical characteristics did not improve the performance of the prediction tool, with similar risk classification distribution, AUCs and negative and positive prediction values.  Despite the strong association between chest radiography findings and active tuberculosis among hospitalised Xpert negative individuals, chest radiography findings did not improve the performance of a risk prediction tool based solely on clinical symptoms. Countries with a high tuberculosis/HIV burden should urgently replace Xpert by the more sensitive Xpert Ultra assay to improve the diagnosis of active tuberculosis.

The role of chest radiography in the diagnosis of bacteriologically confirmed pulmonary tuberculosis in hospitalised Xpert MTB/RIF-negative patients