Background and Objective – In the field of medical image analysis, achieving high accuracy is not enough; ensuring well-calibrated predictions is also crucial. Confidence scores of a deep neural network play a pivotal role in explainability by providing insights into the model's certainty, identifying cases that require attention and establishing trust in its predictions. Consequently, the significance of a well-calibrated model becomes paramount in the medical imaging domain, where accurate and reliable predictions are of utmost importance. While there has been a significant effort towards training modern deep neural networks to achieve high accuracy on medical imaging tasks, model calibration and factors that affect it remain under-explored. Methods – To address this, we conducted a comprehensive empirical study that explores model performance and calibration under different training regimes. We considered fully supervised training, which is the prevailing approach in the community, as well as rotation-based self-supervised method with and without transfer learning, across various datasets and architecture sizes. Multiple calibration metrics were employed to gain a holistic understanding of model calibration. Results – Our study reveals that factors such as weight distributions and the similarity of learned representations correlate with the calibration trends observed in the models. Notably, models trained using rotation-based self-supervised pretrained regime exhibit significantly better calibration while achieving comparable or even superior performance compared to fully supervised models across different medical imaging datasets. Conclusion – These findings shed light on the importance of model calibration in medical image analysis and highlight the benefits of incorporating self-supervised learning approach to improve both performance and calibration. © 2023 Elsevier B.V.