Objectives Digital breast tomosynthesis (DBT) increases sensitivity of mammography and is increasingly implemented in breast cancer screening. However, the large volume of images increases the risk of reading errors and reading time. This study aims to investigate whether the accuracy of breast radiologists reading wide-angle DBT increases with the aid of an artificial intelligence (AI) support system. Also, the impact on reading time was assessed and the stand-alone performance of the AI system in the detection of malignancies was compared to the average radiologist. Methods A multi-reader multi-case study was performed with 240 bilateral DBT exams (71 breasts with cancer lesions, 70 breasts with benign findings, 339 normal breasts). Exams were interpreted by 18 radiologists, with and without AI support, providing cancer suspicion scores per breast. Using AI support, radiologists were shown examination-based and region-based cancer likelihood scores. Area under the receiver operating characteristic curve (AUC) and reading time per exam were compared between reading conditions using mixed-models analysis of variance. Results On average, the AUC was higher using AI support (0.863 vs 0.833; p = 0.0025). Using AI support, reading time per DBT exam was reduced (p < 0.001) from 41 (95% CI = 39–42 s) to 36 s (95% CI = 35– 37 s). The AUC of the stand-alone AI system was non-inferior to the AUC of the average radiologist (+0.007, p = 0.8115). Conclusions Radiologists improved their cancer detection and reduced reading time when evaluating DBT examinations using an AI reading support system. Key Points • Radiologists improved their cancer detection accuracy in digital breast tomosynthesis (DBT) when using an AI system for support, while simultaneously reducing reading time. • The stand-alone breast cancer detection performance of an AI system is non-inferior to the average performance of radiologists for reading digital breast tomosynthesis exams. • The use of an AI support system could make advanced and more reliable imaging techniques more accessible and could allow for more cost-effective breast screening programs with DBT.