This study assesses the usability of the health information system in referral hospitals in Tanzania. The study divided the research participants into two strata, including service providers and service recipients, to ensure balanced opinions. The participants were obtained using a simple random sampling technique. The mixed-research approach was applied to collecting both quantitative and qualitative data. A questionnaire and an unstructured interview guide were used in data collection. The findings revealed that the usability of the health information system at Geita regional referral hospital is adequate, despite a few insights that should be taken into consideration to maximize its usability, quality of service delivery, and increased level of acceptance. The usability factors that were perceived positively include visibility, navigation, and easy retrieval of data. On the other hand, although factors including task-technology match, report generation capability, stock level management notifications, and the ability to manage queues were positively perceived, it was found that a significant percentage of participants were not sure or disagreed. Additionally, despite the usability challenges, the use of the health information system at Geita Regional Referral Hospital has resulted in improved quality of healthcare provision in terms of reduced waiting time, easy and quick patient data retrieval, a proper payment system, and equitable service.