Introduction: Endobronchial ultrasound-guided transbronchial mediastinal cryobiopsy (EBUS-TMC), a novel technique, has been reported to improve the diagnostic value of endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) for mediastinal lesions in recent studies. Current literature suggests that this procedure has greater diagnostic efficacy compared to conventional EBUS-TBNA. This systematic review and meta-analysis aimed to evaluate the diagnostic yield and complications associated with EBUS-TMC in comparison to EBUS-TBNA, thereby exploring the potential of this novel technique in enhancing the diagnostic utility for mediastinal lesions. Methods: A comprehensive literature review was conducted by searching the PubMed, Embase, and Google Scholar databases for articles published from inception to December 31, 2023. The objective of this review was to evaluate the utilization of EBUS-TMC in diagnosing mediastinal disease, while also assessing the quality of each study using the QUADAS-2 tool. The diagnostic yield estimates were subjected to a meta-analysis utilizing inverse variance weighting. Furthermore, a comprehensive analysis of the complications associated with this procedure was performed. Results: The meta-analysis included 10 studies involving a total of 538 patients. The findings of the meta-analysis demonstrated that EBUS-TMC yielded an overall diagnostic rate of 89.59% (482/538), while EBUS-TBNA yielded a rate of 77.13% (415/538). The calculated inverse variance-weighted odds ratio was 2.63 (95% confidence interval, 1.86-3.72; p<0.0001), and I2 value was 11%, indicating a statistically significant difference between the two techniques. The associated complications consisted of pneumothorax, pneumomediastinum, mediastinitis and bleeding, with an incidence of 0.74% (4/538), 0.37% (2/538), 0.0% (0/538), and 1.12% (6/538), respectively. Moreover, the funnel plot displayed no discernible publication bias. Further subgroup analysis revealed a notable improvement in the diagnosis value for lymphoma (86.36% vs. 27.27%, p=0.0006) and benign disorder (87.62% vs. 60.00%, p < 0.0001). Conclusion: This review of the current available studies indicated that EBUS-TMC enhanced overall diagnostic yields compared to EBUS-TBNA, particularly for diagnosing benign disease and lymphoma. This procedure was not associated with any serious complications.