Background Artificial intelligence (AI), conceived in the 1950s, has permeated numerous industries, intensifying in tandem with advancements in computing power. Despite the widespread adoption of AI, its integration into medicine trails other sectors. However, medical AI research has experienced substantial growth, attracting considerable attention from researchers and practitioners. Objective In the absence of an existing framework, this study aims to outline the current landscape of medical AI research and provide insights into its future developments by examining all AI-related studies within PubMed over the past 2 decades. We also propose potential data acquisition and analysis methods, developed using Python (version 3.11) and to be executed in Spyder IDE (version 5.4.3), for future analogous research. Methods Our dual-pronged approach involved (1) retrieving publication metadata related to AI from PubMed (spanning 2000-2022) via Python, including titles, abstracts, authors, journals, country, and publishing years, followed by keyword frequency analysis and (2) classifying relevant topics using latent Dirichlet allocation, an unsupervised machine learning approach, and defining the research scope of AI in medicine. In the absence of a universal medical AI taxonomy, we used an AI dictionary based on the European Commission Joint Research Centre AI Watch report, which emphasizes 8 domains: reasoning, planning, learning, perception, communication, integration and interaction, service, and AI ethics and philosophy. Results From 2000 to 2022, a comprehensive analysis of 307,701 AI-related publications from PubMed highlighted a 36-fold increase. The United States emerged as a clear frontrunner, producing 68,502 of these articles. Despite its substantial contribution in terms of volume, China lagged in terms of citation impact. Diving into specific AI domains, as the Joint Research Centre AI Watch report categorized, the learning domain emerged dominant. Our classification analysis meticulously traced the nuanced research trajectories across each domain, revealing the multifaceted and evolving nature of AI’s application in the realm of medicine. Conclusions The research topics have evolved as the volume of AI studies increases annually. Machine learning remains central to medical AI research, with deep learning expected to maintain its fundamental role. Empowered by predictive algorithms, pattern recognition, and imaging analysis capabilities, the future of AI research in medicine is anticipated to concentrate on medical diagnosis, robotic intervention, and disease management. Our topic modeling outcomes provide a clear insight into the focus of AI research in medicine over the past decades and lay the groundwork for predicting future directions. The domains that have attracted considerable research attention, primarily the learning domain, will continue to shape the trajectory of AI in medicine. Given the observed growing interest, the domain of AI ethics and philosophy also stands out as a prospective area of increased focus.