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Purpose: To examine whether incorporating anatomical awareness into a deep learning model can improve generalizability and enable prediction of disease progression. Methods: This retrospective multicenter study included conventional pelvic radiographs of 4 different patient cohorts focusing on axial spondyloarthritis (axSpA) collected at university and community hospitals. The first cohort, which consisted of 1483 radiographs, was split into training (n=1261) and validation (n=222) sets. The other cohorts comprising 436, 340, and 163 patients, respectively, were used as independent test datasets. For the second cohort, follow-up data of 311 patients was used to examine progression prediction capabilities. Two neural networks were trained, one on images cropped to the bounding box of the sacroiliac joints (anatomy-aware) and the other one on full radiographs. The performance of the models was compared using the area under the receiver operating characteristic curve (AUC), accuracy, sensitivity, and specificity. Results: On the three test datasets, the standard model achieved AUC scores of 0.853, 0.817, 0.947, with an accuracy of 0.770, 0.724, 0.850. Whereas the anatomy-aware model achieved AUC scores of 0.899, 0.846, 0.957, with an accuracy of 0.821, 0.744, 0.906, respectively. The patients who were identified as high risk by the anatomy aware model had an odds ratio of 2.16 (95% CI: 1.19, 3.86) for having progression of radiographic sacroiliitis within 2 years. Conclusion: Anatomical awareness can improve the generalizability of a deep learning model in detecting radiographic sacroiliitis. The model is published as fully open source alongside this study.