Systematic reviews and meta-analyses rank the highest in the evidence hierarchy. However, they still have the risk of spurious results because they include too few studies and participants. The use of trial sequential analysis (TSA) has increased recently, providing more information on the precision and uncertainty of meta-analysis results. This makes it a powerful tool for clinicians to assess the conclusiveness of meta-analysis. TSA provides monitoring boundaries or futility boundaries, helping clinicians prevent unnecessary trials. The use and interpretation of TSA should be based on an understanding of the principles and assumptions behind TSA, which may provide more accurate, precise, and unbiased information to clinicians, patients, and policymakers. In this article, the history, background, principles, and assumptions behind TSA are described, which would lead to its better understanding, implementation, and interpretation.