INTRODUCTION: Examining the evolution of research parameters helps scientists to discover the well-developed and neglected aspects of knowledge. Pain after root canal treatment is a health problem affecting millions of patients. Research in this field has a meaningful impact on quality of lives. The aim of this study was to analyze the evolution of research on postoperative pain over the past 50 years. METHODS: Electronic searches were performed in Scopus and MEDLINE databases to identify studies on pain after nonsurgical root canal treatments/retreatments. The full texts of eligible articles were reviewed to determine the study category and to extract and analyze the methodological variables. A series of statistical analyses were performed to determine the trend of publications based on the variable of interest over time. RESULTS: Four hundred twenty-four articles were included. There was a positive trend for systematic reviews, studies with sample size <200, studies on single-visit treatment, and clinical trials on instrumentation and adjunct treatments (P < .05). There was a negative trend for the use of numeric rating scales, studies on multiple-visit treatments, clinical trials on medication/medicament, and studies on pain in maxillary incisors (P < .05). No trend was observed based on pulpal diagnosis or for studies with longer observation periods (>8 weeks) (P > .05). CONCLUSIONS: A paradigm shift is needed toward clinical studies with larger sample sizes, longer observation periods, and more focus on pulpal diagnoses associated with higher rates of postoperative pain. There is a need to view postoperative pain as an important patient-centered outcome and to develop and disseminate standard reporting guidelines for future studies.