BACKGROUND: Systematic screening for TB using automated chest radiography (ACR) with computer-aided detection software (CAD4TB) has been implemented at scale in Karachi, Pakistan. Despite evidence supporting the use of ACR as a pre-screen prior to Xpert® MTB/RIF diagnostic testing in presumptive TB patients, there has been no data published on its use in mass screening in real-world settings.METHOD: Screening was undertaken using mobile digital X-ray vehicles at hospital facilities and community camps. Chest X-rays were offered to individuals aged ≥15 years, regardless of symptoms. Those with a CAD4TB score of ≥70 were offered Xpert testing. The association between Xpert positivity and CAD4TB scores was examined using data collected between 1 January and 30 June 2018 using a custom-built data collection tool.RESULTS: Of the 127 062 individuals screened, 97.2% had a valid CAD4TB score; 11 184 (9.1%) individuals had a CAD4TB score ≥70. Prevalence of Xpert positivity rose from 0.7% in the <50 category to 23.5% in the >90 category. The strong linear association between CAD4TB score and Xpert positivity was found in both community and hospital settings.CONCLUSION: The strong association between CAD4TB scores and Xpert positivity provide evidence that an ACR-based pre-screening performs well when implemented at scale in a high-burden setting.