Multiple myeloma (MM) is a malignant plasma cell disorder. The most widely accepted staging system for MM is the revised International Staging System based on cytogenetic and clinical biomarkers. The circulating clonal plasma cells (CPCs) were reported to have potential prognostic impact on MM. Among various diagnostic approaches, multiparametric flow cytometry (FCM) offers heightened sensitivity, minimal invasiveness and reproducibility. We conducted a meta-analysis to evaluate the prognostic value of quantifying CPCs via FCM in newly diagnosed symptomatic MM (NDMM) patients.Systematic review and meta-analysis.PubMed, Web of Science, Embase and references of included studies.We included observational studies that evaluated the prognostic value of CPCs detected by FCM in NDMM.Data were screened and extracted independently by two investigators. The pooled results originated from random effects models. The primary endpoint was overall survival (OS). The secondary endpoint was progression-free survival (PFS). To evaluate the prognostic value of CPCs in NDMM, HRs and their 95% CI for both OS and PFS were derived using COX multivariable models. These values were then used to compute the pooled estimated effect.Our meta-analysis encompassed a total of 2704 NDMM patients from 11 studies up to 27 August 2022. The pooled HR for OS and PFS in CPC-positive (CPCs+) group and CPC-negative group were 1.95 (95% CI 1.24 to 3.07) and 2.07 (95% CI 1.79 to 2.39), respectively. The autologous stem cell transplantation (ASCT) failed to eliminate the adverse impact on OS and PFS. The heterogeneity may stem from the use of novel agents or traditional chemotherapy as initial treatment.This meta-analysis indicates CPCs+ had an adverse impact on the prognosis of NDMM patients in the total population, and the adverse impact could not be eliminated by ASCT.CRD42021272381.© Author(s) (or their employer(s)) 2024. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.