To develop deep learning-based cardiac chamber enlargement-detection algorithms for left atrial (DLCE-LAE) and ventricular enlargement (DLCE-LVE), on chest radiographs METHODS: For training and internal validation of DLCE-LAE and -LVE, 5,045 chest radiographs (CRs; 2,463 normal and 2,393 LAE) and 1,012 CRs (456 normal and 456 LVE) matched with the same-day echocardiography were collected, respectively. External validation was performed using 107 temporally independent CRs. Reader performance test was conducted using the external validation dataset by five cardiothoracic radiologists without and with the results of DLCE. Classification performance of DLCE was evaluated and compared with those of the readers and conventional radiographic features, including cardiothoracic ratio, carinal angle, and double contour. In addition, DLCE-LAE was tested on 5,277 CRs from a healthcare screening program cohort. DLCE-LAE showed areas under the receiver operating characteristics curve (AUROCs) of 0.858 on external validation. On reader performance test, DLCE-LAE showed better results than pooled radiologists (AUROC 0.858 vs. 0.651; p < .001) and significantly increased their performance when used as a second reader (AUROC 0.651 vs. 0.722; p < .001). DLCE-LAE also showed a significantly higher AUROC than conventional radiographic findings (AUROC 0.858 vs. 0.535-0.706; all ps < .01). In the healthcare screening cohort, DLCE-LAE successfully detected 71.0% (142/200) CRs with moderate-to-severe LAE (93.5% [29/31] of severe cases), while yielding 11.8% (492/4,184) false-positive rate. DLCE-LVE showed AUROCs of 0.966 and 0.594 on internal and external validation, respectively. DLCE-LAE outperformed and improved cardiothoracic radiologists' performance in detecting LAE and showed promise in screening individuals with moderate-to-severe LAE in a healthcare screening cohort. • Our deep learning algorithm outperformed cardiothoracic radiologists in detecting left atrial enlargement on chest radiographs. • Cardiothoracic radiologists improved their performance in detecting left atrial enlargement when aided by the algorithm. • On a healthcare-screening cohort, our algorithm detected 71.0% (142/200) radiographs with moderate-to-severe left atrial enlargement while yielding 11.8% (492/4,184) false-positive rate.