Objective To explore the differences between large and small studies in rare events meta-analysis. Methods Empirical data were collected from The Cochrane Systematic Review Database from January 2003 to May 2018. Meta-analyses with rare events, binary outcomes involving at least 5 studies, and at least 1 large study were screened. Peto and classical ORs were used to compare the magnitude, direction and P-value. Results A total of 214 meta-analyses were included. Among 214 pairs of ORs of large and small studies, 66 pairs (30.84%) were inconsistent in the direction of ORs based on Peto OR (Kappa =0.33), and 69 pairs (32.24%) were inconsistent in the direction of ORs based on classical OR. The Peto ORs resulted in smaller P-values compared to classic ORs in a substantial (83.18%) number of cases. Conclusion There are considerable differences between large and small studies in the results of meta-analysis of rare events.