Plasma exchange (PE) is a promising therapeutic option in patients with acute liver failure (ALF) and acute-on-chronic liver failure (ACLF). However, the impact of PE on patient survival in these syndromes is unclear. We aimed to systematically investigate the use of PE in patients with ALF and ACLF compared to standard medical therapy (SMT). We searched PubMed/Embase/Cochrane databases to include all studies comparing PE versus SMT for patients > 18 years of age with ALF and ACLF. Pooled risk-ratios (RR) with corresponding 95% confidence intervals (CIs) were calculated by Mantel-Haenszel method within a random-effect model. Primary outcome was 30-day survival for ACLF and ALF. Secondary outcomes were overall and 90-day survival for ALF and ACLF, respectively. Five studies, including 343 ALF patients (n = 174 PE vs. n = 169 SMT), and 20 studies, including 5,705 ACLF patients (n = 2,856 PE vs. n = 2,849 SMT), were analyzed. Compared to SMT, PE was significantly associated with higher 30-day (RR 1.41, 95%CI 1.06-1.87, p = 0.02) and overall (RR 1.35, 95%CI 1.12-1.63, p = 0.002) survival in ALF patients. In ACLF, PE was also significantly associated with higher 30-day (RR 1.36, 95%CI 1.22-1.52, p < 0.001) and 90-day (RR 1.21, 95%CI 1.10-1.34, p < 0.001) survival. On subgroup analysis of randomized controlled trials (RCT), results remained unchanged in ALF but no differences in survival were found between PE and SMT in ACLF. In conclusion, PE is associated with improved survival in ALF and could improve survival in ACLF. PE may be considered in managing ALF and ACLF patients who are not liver transplant (LT) candidates, or as a bridge to LT in otherwise eligible patients. Further RCTs are needed to confirm the survival benefit of PE in ACLF.