SUMMARY Recently, novel machine-learning algorithms have shown potential for predicting undiscovered links in biomedical knowledge networks. However, dedicated benchmarks for measuring algorithmic progress have not yet emerged. With OpenBioLink, we introduce a large-scale, high-quality and highly challenging biomedical link prediction benchmark to transparently and reproducibly evaluate such algorithms. Furthermore, we present preliminary baseline evaluation results. AVAILABILITY AND IMPLEMENTATION Source code and data are openly available at https://github.com/OpenBioLink/OpenBioLink. SUPPLEMENTARY INFORMATION Supplementary data are available at Bioinformatics online.