AbstractMotivationAgent-based modeling is an indispensable tool for studying complex biological systems. However, existing simulators do not always take full advantage of modern hardware and often have a field-specific software design.ResultsWe present a novel simulation platform called BioDynaMo that alleviates both of these problems. BioDynaMo features a general-purpose and high-performance simulation engine. We demonstrate that BioDynaMo can be used to simulate use cases in: neuroscience, oncology, and epidemiology. For each use case we validate our findings with experimental data or an analytical solution. Our performance results show that BioDynaMo performs up to three orders of magnitude faster than the state-of-the-art baseline. This improvement makes it feasible to simulate each use case with one billion agents on a single server, showcasing the potential BioDynaMo has for computational biology research.AvailabilityBioDynaMo is an open-source project under the Apache 2.0 license and is available atwww.biodynamo.org. Instructions to reproduce the results are available in supplementary information.Contactlukas.breitwieser@inf.ethz.ch,a.s.hesam@tudelft.nl,omutlu@ethz.ch,r.bauer@surrey.ac.ukSupplementary informationAvailable athttps://doi.org/10.5281/zenodo.4501515.