The artificial liver support system (ALSS) offers the potential to improve the prognosis of patients with acute-on-chronic liver failure (ACLF). However, the literature has been inconsistent on its survival benefits. We aimed to conduct a time series-based meta-analysis of randomized clinical trials (RCTs) and observational studies which examined differences in mortality in ACLF patients treated with ALSS or not.MEDLINE, EMBASE, OVID, and COCHRANE library database were systemically searched up to December 2014. Quality of included studies was evaluated using the Jadad score. The outcome measure was mortality at different follow-up endpoints. Odds ratios (ORs) and survival curve data were pooled for analysis.Ten studies, 7 RCTs, and 3 controlled cohorts were enrolled, involving a total of 1682 ACLF patients, among whom 842 were treated with ALSS. ALSS was found to reduce the risk of short-term (1-month and 3-month) mortality for patients with ACLF by nearly 30%. Randomized trials and observational studies provided good internal and external validity respectively. The combined Kaplan-Meier curves showed a consistent pattern of findings. Meta-analysis also suggested that ALSS might reduce medium-term (6-month and 1-year) mortality risk by 30% and long-term (3-year) mortality risk by 50% in ACLF patients.ALSS therapy could reduce short-term mortality in patients with ACLF. Meanwhile, its impacts on medium- and long-term survival seem to be promising but remained inconclusive. Clinical utility of this system for survival benefit may be implied.