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Objective: To systematically evaluate and analyze the original research of prescription sequence symmetry analysis (PSSA), summarize its research progress and methodological details, and provide a reference for the future use of this method. Methods: The keywords related to PSSA were used for literature retrieval from Chinese databases (CNKI, Wanfang, and VIP) and English databases (PubMed, Embase, and Cochrane). Original articles that were related to PSSA and published before June 30, 2020 were selected. Information form was developed by Excel. Stata was used for the statistics analysis. Results: There were 45 eligible articles included in the research. Since 2013, the number of studies using PSSA has increased rapidly. These studies were mainly conducted in Japan ( n =11, 24.44%), China ( n =10, 22.22%), Denmark ( n =9, 20.00%), and Australia ( n =8, 17.78%). Medical claim database was used most commonly when PSSA was implemented. The included studies involved 16 types of drugs, of which the number of studies of psychotropic drugs and statins was highest ( n =8, 17.78%), and adverse reactions of almost all human systems were involved. In terms of methodology, 35 (77.78%) and 43 (95.56%) studies clearly reported the run-in period and interval period, of which 14 (31.11%) and 9 (20.00%) respectively gave the method or reason for determining the duration. In addition, 16 articles (35.56%) and 18 articles (40.00%) reported sensitivity analysis and subgroup analysis results, respectively. Conclusions: PSSA, one of the effective methods for safety signal detection in healthcare databases, has developed rapidly, but the methodological details and result reporting need to be improved. In China, PSSA research is still in its infancy, and it is necessary to pay attention to the quality of research and promote methodological exploration.