Background The risk factors for central venous access device-related thrombosis (CRT) in children are not fully understood. We used evidence-based medicine to find the risk factors for CRT by pooling current studies reporting risk factors of CRT, aiming to guide clinical diagnosis and treatment.Methods A systematic search of PubMed, Web of Science, Embase, Cochrane Library, Scopus, CNKI, Sinomed, and Wanfang databases was conducted. RevMan 5.4 was employed for data analysis.Results The review included 47 studies evaluating 262,587 children with CVAD placement. Qualitative synthesis and quantitative meta-analysis identified D-dimer, location of insertion, type of catheter, number of lumens, catheter indwelling time, and central line-associated bloodstream infection as the most critical risk factors for CRT. Primarily due to observational design, the quality of evidence was regarded as low certainty for these risk factors according to the GRADE approach.Conclusion Because fewer high-quality studies are available, larger sample sizes and well-designed prospective studies are still needed to clarify the risk factors affecting CRT. In the future, developing pediatric-specific CRT risk assessment tools is important. Appropriate stratified preventive strategies for CRT according to risk assessment level will help improve clinical efficiency, avoid the occurrence of CRT, and alleviate unnecessary suffering of children.Impact This is the latest systematic review of risk factors and incidence of CRT in children. A total of 47 studies involving 262,587 patients were included in our meta-analysis, according to which the pooled prevalence of CRT was 9.1%. This study identified several of the most critical risk factors affecting CRT in children, including D-dimer, insertion location, type of catheter, number of lumens, catheter indwelling time, and central line-associated bloodstream infection (CLABSI).