Objectives: This study aims to evaluate the success rate of formocresol and ferric sulfate through meta-analysis with trial sequential analysis (TSA). Method and materials: The protocol of the review was registered in the PROSPERO database (CRD 42018090044). Two independent reviewers used PubMed, Scopus and EBSCOhost databases to identify randomized clinical trials published from inception to June 2019. Patients undergoing pulpotomy therapy in vital primary molars with pulp exposure due to caries treated with formocresol and ferric sulfate were evaluated for clinical and radiographic success. Meta-analysis was conducted to evaluate the success at 6, 12, 18, and 24 months and TSA was performed for success at 24 months. Quality of evidence was determined by Grading of Recommendations, Assessment, Development, and Evaluations (GRADE) analysis. Results: Eight clinical trials were included in meta-analysis. No difference was observed in the clinical and radiographic success rate between formocresol and ferric sulfate at 6, 12, 18, and 24 months. TSA identified required information size of 687 teeth for clinical success and 568 teeth for radiographic success. In addition, it demonstrated evidence for radiographic success rate at an anticipated intervention effect of 10% for formocresol over ferric sulfate. Conclusion: Formocresol and ferric sulfate show comparable clinical and radiographic success rates as pulpotomy material in primary molars at 24 months based on the studies with low to moderate quality of evidence. Keywords: ferric sulfate, formocresol, pulpotomy, systematic review, trial sequential analysis