Clinical databases, particularly those composed of big data, face growing security challenges. Blockchain, the open, decentralized, distributed public ledger technology powering cryptocurrency, records transactions securely without the need for third-party verification. In the health care setting, decentralized blockchain networks offer a secure interoperable gateway for clinical research and practice data. Here, we discuss recent advances and potential future directions for the application of blockchain and its integration with artificial intelligence (AI) in cardiovascular medicine. We first review the basic underlying concepts of this technology and contextualise it within the spectrum of current, well known applications. We then consider specific applications for cardiovascular medicine and research in areas such as high-throughput gene sequencing, wearable technologies, and clinical trials. We then evaluate current challenges to effective implementation and future directions. We also summarise the health care applications that can be realised by combining decentralized blockchain computing platforms (for data security) and AI computing (for data analytics). By leveraging high-performance computing and AI capable of securely managing large and rapidly expanding medical databases, blockchain incorporation can provide clinically meaningful predictions, help advance research methodology (eg, via robust AI-blockchain decentralized clinical trials), and provide virtual tools in clinical practice (eg, telehealth, sensory-based technologies, wearable medical devices). Integrating AI and blockchain approaches synergistically amplifies the strengths of both technologies to create novel solutions to serve the objective of providing precision cardiovascular medicine.