SummaryThe AutoScore framework can automatically generate data-driven clinical scores in various clinical applications. Here, we present a protocol for developing clinical scoring systems for binary, survival, and ordinal outcomes using the open-source AutoScore package. We describe steps for package installation, detailed data processing and checking, and variable ranking. We then explain how to iterate through steps for variable selection, score generation, fine-tuning, and evaluation to generate understandable and explainable scoring systems using data-driven evidence and clinical knowledge.For complete details on the use and execution of this protocol, please refer to Xie et al. (2020),1Xie et al. (2022)2, Saffari et al. (2022)3and the online tutorialhttps://nliulab.github.io/AutoScore/.