Background: Medicine supply management consist four basic functions of medicine management cycle which are selection, procurement, inventory management and serving customers/use. Poor medicine management practice results shortages of essential medicines, high prices, poor quality, theft, expiration, irrational prescribing, and incorrect use of medicines by patients. In Ethiopia although the medicine supply chain has several problems; studies dedicated to assess these medicine management problems are limited. Therefore, the aim of this study is to assess the medicine supply management and its quality assurance practice in selected health centers of South West Shoa zone, Oromia, Ethiopia. Methods: A facility based cross-sectional survey through quantitative data collection method was conducted in 10 health centers from March 1 to 12, 2018. Structured-questionnaires and observation check lists were used to collect data. The data was analyzed using SPSS version 23.0. Results: In most HCs (n=8) selection was not decided by drug and therapeutic committee with the use of essential medicine lists. All HCs reported that items and quantities were sent by suppliers without determining what the specific need. In all HCs there were no a supply planning used for procurement. 9 HCs didn't have facility vehicle/ Car for transportation of medicines. The median percent adequacy of storage conditions in all HC store rooms was found to be 50%. All the HCs reported to use bin cards in store. However, only one of the HC had stock cards and automated recoding systems. Conclusion: The practice of medicine supply management in health centers of South West Shoa Zone was found poor. Moreover in majority of the surveyed health centers there were deficiencies in medicines selection, quantification, procurement, storage and quality assurance practices. Health centers therefore should work in collaboration with other stakeholders to strengthen/develop a way to have strong medicine supply management and a monitoring and evaluation system.