The Assay for Transposase Accessible Chromatin with high-throughput sequencing or ATAC-seq, is a method for mapping genome-wide chromatin accessibility. Sequencing reads can be used to determine regions of increased accessibility, in addition to identifying locations of transcription factor binding and nucleosome position. Analysis of ATAC-seq data is most commonly performed using peak calling methods such as MACS2 or HOMER, which are ideal when the aim is to find accessible genomic regions. However, when performing a differential analysis between groups of samples, this approach may not be the most appropriate. It has been shown that calling peaks on individual samples or groups can cause a loss of error rate control during a differential analysis. Here we present two alternative approaches to ATAC-seq data analysis that overcome this difficulty. The first is a gene based approach where we focus on accessibility changes in the promoter region of all genes. This method is fast and easy to perform, as well as easily relatable to other sequencing technologies such as RNA-seq. The second approach applies the Bioconductor package CSAW which utilises sliding windows to analyse changes genome-wide. These methods are demonstrated and compared with the peak calling approach using an ATAC-seq data set that comprises mouse wild type and Tcf7 knock-out double negative 3 cells.