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Background: Breast cancer has a 14.8% incidence rate and an 8.5% fatality rate in Saudi Arabia. Mammography is useful for the early detection of breast cancer. Researchers have been developing artificial intelligence (AI) algorithms for early breast cancer diagnosis and reducing false-positive mammography results. The aim of this study was to examine the performance and accuracy of an AI system in breast cancer screening among Saudi women. Materials and Methods: This is a retrospective cross-sectional study that included 378 mammograms collected from 2017 to 2021 from government hospitals in Jeddah, Saudi Arabia. The patients’ demographic and clinical information were collected from files and electronic medical records. The radiologists’ assessments of the mammograms were based on Breast Imaging Reporting and Data System (BIRADS) scores. Follow-up or biopsy reports verified the radiologists’ findings. The MammoScreen system was the AI tool used in this study. Data were analyzed using SPSS Version 25. Results: The patients’ mean age was 50.31 years. Most patients had breast density B (42.3%) followed by A (27.2%) and C (25.9%). Most malignant cases were invasive ductal carcinomas (37.3%). Of the 181 cancer cases, 36.9% were BIRADS category V. The area under the curve for the AI detection (0.923; 95% confidence interval [CI], 0.893–0.954) was greater than that for the radiologists’ interpretation (0.838; 95% CI, 0.796–0.881). The AI detection agreed with the histopathological result in 167 positive (91.3%) and 182 negative cases (93.3%). The sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV), and accuracy of the AI system were 92.8%, 91.9%, 91.3%, 93.3%, and 92.3%, respectively. The radiologist’s interpretation agreed with the pathology report in 180 positive (73.8%) and 134 negative cases (100%). Its sensitivity, specificity, PPV, NPV, and accuracy were 100%, 67.7%, 73.8%, 100%, and 83.1%, respectively. Conclusions: The AI system tested in this study had better accuracy and diagnostic performance than the radiologists and thus could be used as a support diagnostic tool for breast cancer detection in clinical practice and to reduce false-positive recalls.