Trichomonas vaginalis , the most common non-viral sexually transmitted parasite, causes more than 270 million infections annually. The infection's outcome varies greatly depending on different factors that include variation in human immune responses, the vaginal microbiome, and the inherent virulence of the strain. Although the pathogenicity of the different strains depends, at least partially, on differential gene expression of virulence genes; the regulatory mechanisms governing this transcriptional control remain incompletely understood. While many studies have reported a positive correlation between gene expression and chromatin accessibility in other cells, this relationship has not been analyzed in T. vaginalis . To address these questions, we selected two contrasting T. vaginalis strains based on their interactions with host cells: B7268 strain, a highly adherent one and resistant to metronidazole, and NYH209 strain, a poorly adherent one and sensitive to metronidazole. Next, we combined the assay for transposase-accessible chromatin using sequencing (ATAC-seq) with RNA sequencing (RNA-seq), to delve into the relationship between chromatin accessibility and gene expression in these distinct T. vaginalis strains. Our findings demonstrate a correlation between chromatin accessibility and gene expression across both strains. Moreover, we found that chromatin accessibility plays a pivotal role in modulating mRNA expression levels of several established genes linked to parasite pathogenesis and drug resistance. We also identified several open chromatin peaks residing at intergenic regions, revealing possible distal regulatory elements that may control gene expression. These results highlight the importance of chromatin accessibility in modulating gene expression in the parasite T. vaginalis , with possible consequences in pathogenesis and/or drug treatment.