SummaryBackground: Medication is the major weapon for successful prevention and treatment of illnesses in modern societies. This makes access to effective medicines and their rational use fundamental to the provision of universal access to adequate health care, satisfying health-related human rights and attaining health-related Millennium Development Goals. However, lack of access to essential medicines is a major cause of loss of lives in developing countries. Almost 1.7 billion people; 30 % of the world population lack regular access to essential medicines, and in Africa this figure goes over 50 %.Out of stock of essential medicines is one of the barriers of access to essential medicines in developing countries including Malawi. Commonly, out of stock situations of essential medicines occur at the health centres level. The consequences of out of stock situations of essential medicines include prolonged suffering of people, loss of both family and government income and more painfully loss of lives due to preventable and treatable diseases. This study, conducted in eight health centres in Lilongwe district in Malawi, addresses the out of stock situations of essential medicines in the distribution system at the health centre level. Objectives: The main objective of the study was to find the magnitude of essential medicines shortage and identify factors that could explain the shortage at health centre level in Lilongwe district, Malawi.Methods: The study was retrospective and cross sectional using both quantitative and qualitative methods. Reviews of essential medicines and patient records were done in eight health centres with eight selected essential medicines as markers. Relevant newspaper articles were also reviewed. In addition, structured and informal interviews with relevant personnel were conducted. Data analysis was done using Microsoft Excel and the Software Package for Social Scientists (SPSS). Results: The study confirms that essential medicines shortage is a major public health problem at health centre level in Lilongwe district, Malawi. Retrospectively, the eight medicines were out of stock for 34.2% (7,141 days) of the total observation period of 20,880 days. In other words, on average the eight index medicines were out of stock for 123.2 days (34.2%) of Malawi s financial year 1 July 2004 to 30 June 2005. The cross sectional findings confirmed that the eight index medicines were out of stock in 43 (67.2%) out of the 64 assessments. The out of stock situations of the essential medicines varied more than 3-fold among the health centres, from 5.3 % in health centre number 7 to 18.3 % in health centre number 6 and 7 times among the medicines, from 3.3% for pyrimethamine + sulfadoxine to 23.1% for benzyl penicillin. The study identified a low number of normal deliveries received by the health centres, increased frequency and long duration of out of stock situations, the number of days some medicines were out of stock and low catchment population as predictors of the number of days the medicines were out of stock. In addition, lack of training and supervision for health workers managing essential medicines, poor ability by the Regional Medical Stores (RMS) to supply requested amounts of medicines and theft were found to be other possible factors that could contribute to the out of stock situations.Oral medicines were better provided than the injectable medicines. The average utilisation difference between the stock cards and the patient records was 65.9 %. This means that of the total amount of medicines received by the health centres, only 1/3 were recorded in the patients records. The discrepancies between the stock cards and the patient records were substantial for amoxicillin and chloramphenicol. Conclusions: The findings suggest that access to essential medicines is a major public health problem in Lilongwe district health centres. With this situation, it is difficult for the district to contribute effectively towards attaining the universal access to adequate health care, satisfying the health-related human rights and attaining the health-related Millennium Development Goals. It is important that interventions to improve access to essential medicines are implemented if the district is to improve the quality of care in the health centres and contribute positively towards the health related Millennium Development Goals.