The development of deep learning algorithms for complex tasks in digital medicine has relied on the availability of large labeled training datasets, usually containing hundreds of thousands of examples. The purpose of this study was to develop a 3D deep learning model, AppendiXNet, to detect appendicitis, one of the most common life-threatening abdominal emergencies, using a small training dataset of less than 500 training CT exams. We explored whether pretraining the model on a large collection of natural videos would improve the performance of the model over training the model from scratch. AppendiXNet was pretrained on a large collection of YouTube videos called Kinetics, consisting of approximately 500,000 video clips and annotated for one of 600 human action classes, and then fine-tuned on a small dataset of 438 CT scans annotated for appendicitis. We found that pretraining the 3D model on natural videos significantly improved the performance of the model from an AUC of 0.724 (95% CI 0.625, 0.823) to 0.810 (95% CI 0.725, 0.895). The application of deep learning to detect abnormalities on CT examinations using video pretraining could generalize effectively to other challenging cross-sectional medical imaging tasks when training data is limited.Appendicitis is one of the most common life-threatening abdominal emergencies, with lifetime risk of ranging from 5-10% and an annual incidence of 90-140 per 100,000 individuals 1-3 . Treatment, via appendectomy, remains the most frequently performed surgical intervention in the world 4 . Computed tomography (CT) imaging of the abdomen is the primary imaging modality to make the diagnosis of appendicitis, exclude other etiologies of acute abdominal pain, and allow for surgical planning and intervention. Because a delay in the time between CT imaging diagnosis and surgical appendectomy can worsen patient outcomes 5-9 , there is increasing pressure on hospital systems to provide 24-7 access to advanced imaging and to ensure that the results of urgent findings, such as appendicitis, are rapidly and accurately communicated to the referring physician 10,11 . However, providing rapid and accurate diagnostic imaging is increasingly difficult to sustain for many medical systems and radiology groups as utilization has rapidly expanded; for example, the CT utilization rate in the emergency room increased from 41 per 1000 in 2000 to 74 per 1000 in 2010, with abdominal CTs accounting for over half of this volume 12,13 . Development of automated systems could potentially help improve diagnostic accuracy and reduce time to diagnosis, thereby improving the quality and efficiency of patient care.Recent advancements in deep learning have enabled algorithms to automate a wide variety of medical tasks [14][15][16][17][18][19][20] . A key aspect for the success of deep learning models on these tasks is the availability of large labeled datasets of medical images 21 , usually containing hundreds of thousands of examples. However, it is challenging to curate large labeled medical imaging dat...