Background <p>Therapeutic plasma exchange (TPE) has emerged as a promising treatment option for pediatric liver failure (PLF) either as a standalone therapy or as a bridge to liver transplant; however, its precise impact on survival outcomes has not been investigated systematically to date. This meta-analysis aims to evaluate the&#xa0;effect of TPE on survival of pediatric patients with liver failure.&#xa0;</p> Methods <p>PubMed, Scopus and Embase databases were searched to include all studies till August 2024 reporting the effect of TPE on survival of acute and acute-on-chronic liver failure patients of age &lt; 18&#xa0;years. Primary outcome measures were overall survival (OS) and transplant-free survival (TFS) at Day ≥ 28 in pediatric acute liver failure (PALF) and pediatric acute-on-chronic liver failure (pACLF) patients undergoing TPE. The secondary outcome measure was to determine changes in biochemical parameters (international nrmalized ratio [INR], bilirubin and ammonia) pre and post-TPE in them.</p> Results <p>Twelve studies (8 = exclusive PALF cohorts and 4 = combined PALF + pACLF cohorts) comprising 310 patients (273 = PALF and 37 = pACLF) who received TPE were included. Pooled OS at Day ≥ 28 for PLF after TPE is 61% (95% CI: 55–66%, <i>p</i> = 0.03, I² = 49%). The estimated pooled TFS in them was 35% (95% CI: 29–41%, <i>p</i> = &lt; 0.01, I² = 84%). On sub-group analysis, the standard-volume TPE group had both higher OS and TFS in comparison to the high-volume sub-group. There was a significant improvement in all three biochemical parameters post-TPE compared to pre-TPE values. None of the included studies reported any TPE-related mortality or potentially fatal side effects.</p> Conclusion <p>TPE shows the potential to improve overall survival in pediatric liver failure, mostly acting as a bridge to liver transplant or native liver recovery. Further, well-designed, adequately powered, randomized-controlled trials are needed to confirm TPE's survival benefit in PLF.</p> Graphical Abstract <p></p>