Background and aim Despite improving the 10-year disease-free-survival, prophylactic central neck dissection (pCND) in differentiated thyroid carcinoma (DTC) should only be considered in patients with high risk factors for lymph node (LN) metastasis due to the increases in the risk of postoperative complications. Our aim was to identify the risk factors for central lymph node metastasis (CLNM) in DTC. Method We searched PubMed, Scopus, Web of science, Cochrane library for eligible studies from inception to November 1, 2021 and a systematic review and meta-analysis were carried out to identify the risk factors for CLNM in DTC. Results We included 41 studies with total of 27,741 patients in this study. The pooled results in this meta-analysis showed that these risk factors were significantly associated with CLNM: age < 45 years (odds ratio (OR) 1.64, 95% confidence interval (CI) 1.34–1.99, p < 0.00001), male sex (OR 1.73, 95% CI 1.54–1.93, p < 0.00001), multifocality (OR 1.87, 95% CI 1.59–2.19, p < 0.00001), bilateral disease (OR 1.43, 95% CI 1.15–1.78, p < 0.001), capsular invasion (OR 1.67, 95% CI 1.10–2.54, p < 0.02), lymphovascular invasion (OR 4.89, 95% CI 2.76–8.66, p < 0.00001) and extra-thyroidal extension (OR 2.43, 95% CI 1.97–3.00, p < 0.00001). In addition, young age (< 45 years), male sex, multifocality, and extra-thyroidal extension were significantly associated with large-volume CLNM in clinically N0 DTC patients. However, the presence of Hashimoto’s thyroiditis was not a predictors of large-volume CLNM. Conclusion Young age (< 45 years), male sex, bilateral disease, multifocality, capsular invasion, lymphovascular invasion and extra-thyroidal extension are significantly associated with CLNM and pCND would be expected to have a higher yield in patients with these risk factors.