The COVID-19 pandemic has had a substantial and global impact on health care, and has greatly accelerated the adoption of digital technology. One of these emerging digital technologies, blockchain, has unique characteristics (eg, immutability, decentralisation, and transparency) that can be useful in multiple domains (eg, management of electronic medical records and access rights, and mobile health). We conducted a systematic review of COVID-19-related and non-COVID-19-related applications of blockchain in health care. We identified relevant reports published in MEDLINE, SpringerLink, Institute of Electrical and Electronics Engineers Xplore, ScienceDirect, arXiv, and Google Scholar up to July 29, 2021. Articles that included both clinical and technical designs, with or without prototype development, were included. A total of 85 375 articles were evaluated, with 415 full length reports (37 related to COVID-19 and 378 not related to COVID-19) eventually included in the final analysis. The main COVID-19-related applications reported were pandemic control and surveillance, immunity or vaccine passport monitoring, and contact tracing. The top three non-COVID-19-related applications were management of electronic medical records, internet of things (eg, remote monitoring or mobile health), and supply chain monitoring. Most reports detailed technical performance of the blockchain prototype platforms (277 [66·7%] of 415), whereas nine (2·2%) studies showed real-world clinical application and adoption. The remaining studies (129 [31·1%] of 415) were themselves of a technical design only. The most common platforms used were Ethereum and Hyperledger. Blockchain technology has numerous potential COVID-19-related and non-COVID-19-related applications in health care. However, much of the current research remains at the technical stage, with few providing actual clinical applications, highlighting the need to translate foundational blockchain technology into clinical use.