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Purpose: Radiological reporting is transitioning to quantitative analysis, requiring large-scale multi-center validation of biomarkers. A major prerequisite and bottleneck for this task is the voxelwise annotation of image data, which is time-consuming for large cohorts. In this study, we propose an iterative training workflow to support and facilitate such segmentation tasks, specifically for high-resolution thoracic CT data., Methods: Our study included 132 thoracic CT scans from clinical practice, annotated by 13 radiologists. In three iterative training experiments, we aimed to improve and accelerate segmentation of the heart and mediastinum. Each experiment started with manual segmentation of 5-25 CT scans, which served as training data for a nnU-Net. Further iterations incorporated AI pre-segmentation and human correction to improve accuracy, accelerate the annotation process, and reduce human involvement over time., Results: Results showed consistent improvement in AI model quality with each iteration. Resampled datasets improved the Dice similarity coefficients for both the heart (DCS 0.91 [0.88; 0.92]) and the mediastinum (DCS 0.95 [0.94; 0.95]). Our AI models reduced human interaction time by 50 % for heart and 70 % for mediastinum segmentation in the most potent iteration. A model trained on only five datasets achieved satisfactory results (DCS > 0.90)., Conclusions: The iterative training workflow provides an efficient method for training AI-based segmentation models in multi-center studies, improving accuracy over time and simultaneously reducing human intervention. Future work will explore the use of fewer initial datasets and additional pre-processing methods to enhance model quality., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)