Purpose: To develop a fully automated algorithm for spleen segmentation and to assess the performance of this algorithm in a large dataset. Materials and Methods: In this retrospective study, a three-dimensional deep learning network was developed to segment the spleen on thorax-abdomen CT scans. Scans were extracted from patients undergoing oncologic treatment from 2014 to 2017. A total of 1100 scans from 1100 patients were used in this study, and 400 were selected for development of the algorithm. For testing, a dataset of 50 scans was annotated to assess the segmentation accuracy and was compared against the splenic index equation. In a qualitative observer experiment, an enriched set of 100 scan-pairs was used to evaluate whether the algorithm could aid a radiologist in assessing splenic volume change. The reference standard was set by the consensus of two other independent radiologists. A Mann-Whitney U test was conducted to test whether there was a performance difference between the algorithm and the independent observer. Results: The algorithm and the independent observer obtained comparable Dice scores (P = .834) on the test set of 50 scans of 0.962 and 0.964, respectively. The radiologist had an agreement with the reference standard in 81% (81 of 100) of the cases after a visual classification of volume change, which increased to 92% (92 of 100) when aided by the algorithm. Conclusion: A segmentation method based on deep learning can accurately segment the spleen on CT scans and may help radiologists to detect abnormal splenic volumes and splenic volume changes.