The paper aims to systematically review the literature on Lean, Six Sigma, Lean Six Sigma (LSS) intervention and its tools and techniques to reduce the medication errors in hospitals. Subject-specific journals according to the top journal ranking lists in the Business School and Healthcare sector were used for the assessment. Eight databases including Medline, PubMed, EBSCOhost, Web of Knowledge, Scopus, Embase, CINAHL and PsycINFO were used to collect relevant articles from the year 1996–2016. A total of 24 studies were identified have from the search meeting the criteria for the systematic literature review. Increased interest in the application of process excellence methodologies such as Lean, Six Sigma and LSS to reduce medication errors especially from the developed countries was found. Several themes have emerged in this paper including: tools and techniques of Lean and Six Sigma in the context of medication errors, Lean and Six Sigma methodology, types of medication errors, LSS project selection, benefits, challenges and success factors. The study is expected to benefit healthcare practitioners in implementing the LSS methodology to reduce medication errors. © 2018, © 2018 Informa UK Limited, trading as Taylor & Francis Group.