Abstract Summary Decoding the properties of immune repertoires is key to understanding the adaptive immune response to challenges such as viral infection. One important quantitative property is differential usage of Ig genes between biological conditions. Yet, most analyses for differential Ig gene usage are performed qualitatively or with inadequate statistical methods. Here we introduce IgGeneUsage, a computational tool for the analysis of differential Ig gene usage. IgGeneUsage employs Bayesian inference with hierarchical models to analyze complex gene usage data from high-throughput sequencing experiments of immune repertoires. It quantifies differential Ig gene usage probabilistically and avoids some common problems related to the current practice of null-hypothesis significance testing. Availability and implementation IgGeneUsage is an R-package freely available as part of Bioconductor at: https://bioconductor.org/packages/IgGeneUsage/. Contact simo.kitanovski@uni-due.de Supplementary information Supplementary data are available at Bioinformatics online.