Background: Essential Medicines (EMs) are medicines that satisfy the priority health care of the population. They are selected with due regard to public health relevance, evidence on efficacy and safety, and comparative cost-effectiveness. While Health Information System (HIS) is a system that integrates data collection, processing, reporting and use of the information necessary for improving health service effectiveness and efficiency through better management at all levels of health services. Method: A cross sectional study was conducted from April to June 2009 in Mbeya Region and at the national level to assess the factors affecting utilization of evidence based health information system for effective supply chain of EMs in Tanzania so as to develop strategies for valuable procurement at the facility and national levels. Quantitative data was collected from 33 health facilities (HFs) and qualitative data was collected from two focus group discussions and 23 different key informants from different levels of the EMs supply chain. Results: This study revealed the following main factors that affect utilisation and management of information system (IS): lack of strong IS at Medical Store Department and Ministry of Health and Social Welfare to manage the organization, suppliers and clients needs; lack of compliance to the national ordering and deliveries guideline and procedures; inadequate funds; low capacity in implementing integrated logistic system; lack of national representative data during annual budgeting and forecasting of EMs requirements; and political interests. Conclusion: In this study the supply chain of EMs at the HFs and central levels in Tanzania is not evidence-based. For effective utilization of HIS in the supply chain of EMs there is need to strengthen the capacity in the management and utilisation of HIS at facility, district and national levels.