OBJECTIVE： To investigate the reasons for drug shortage in medical institutions of Sichuan province and put forward relevant countermeasures， and to provide reference for establishing supply security mechanism of drug shortage. METHODS： Questionnaire survey was conducted to investigate drug shortage in 78 medical institutions of the province during Jan. 2015-Jun. 2017. Traceability investigation was conducted from manufacturers and distribution enterprises involved in drug shortage. Questionnaire survey and field investigation were combined to analyze the reasons for drug shortage in Sichuan province and put forward countermeasures. RESULTS： Totally 78 questionnaires were sent out to medical institutions with recovery rate and effective rate of 100％. A total of 206 drugs were reported by 78 medical institutions， involving 240 specifications for shortage in total. Totally 140 questionnaires and 68 questionnaires were distributed to the manufacturers and distribution enterprises involved in drug shortage， and the recovery rate and effective rate were all 100％. Combined with the field survey， survey results of shortage drugs of 212 specifications were obtained. From the perspective of manufacturers， the most important factors causing drug shortage were the increase of production cost （66.51％） and circulation cost（26.88％）. From the perspective of distribution enterprises，the main factors causing drug shortage were insufficient supply of drugs（75.47％），inventory management（16.51％） and price inversion（11.32％）. CONCLUSIONS： Main reasons of drug shortage from manufacturers and distribution enterprises include the increase of production cost and circulation cost， drug price inversion， inventory management and bidding procurement. It is suggested that measures should be taken to improve the bidding and pricing system of drugs， mobilize the enthusiasm of enterprises； improve the early warning mechanism of drug shortage on the enterprises， strengthen information communication； establish the mechanism of drug shortage reserve， organize the emergency production of drug for shortage； strengthen the management of drug shortage supply chain， purify the unhealthy atmosphere in the market； improve the emergency disposal methods of drug shortage， and improve the supply guarantee ability of drug shortage. Departments cooperate to reduce the emergence of drug shortage and ensure the continuous access to safe and effective drugs in clinic.