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Several studies have reported a survival benefit for polymyxin B hemoperfusion treatment in patients with severe sepsis and septic shock. However, recently, a propensity-matched analysis and a randomized controlled trial reported no survival benefit for polymyxin B hemoperfusion treatment. We performed an up-to-date meta-analysis to determine the effect of polymyxin B hemoperfusion treatment on mortality in patients with severe sepsis and septic shock.PubMed, Embase, and Cochrane Library were searched from inception to May 2016.Studies investigating the effect of polymyxin B hemoperfusion on mortality were considered eligible. We searched for terms related to severe sepsis and septic shock and terms related to polymyxin B hemoperfusion.The following data were extracted from the original articles: the name of the first author and publication year, subjects and setting, inclusion and exclusion criteria, mean age and size of the study population, male percentage, mortality, blood pressure, Sequential Organ Failure Assessment score, pulmonary oxygenation, and levels of endotoxin and humoral cytokines.A total of 17 trials were included. The pooled risk ratio for overall mortality was 0.81 (95% CI, 0.70–0.95), favoring polymyxin B hemoperfusion (p = 0.007). Disease severity subgroup meta-analysis revealed a significant reduction of mortality in the intermediate- and high-risk groups (risk ratio, 0.84; 95% CI, 0.77–0.92 and risk ratio, 0.64; 95% CI, 0.52–0.78, respectively), but not in the low-risk group (risk ratio, 1.278; 95% CI, 0.888–1.839). The nonlinear meta-regression with restricted cubic spline showed an almost linear inverse association between the baseline mortality rate and reduction in the risk of mortality.The present study demonstrated that polymyxin B hemoperfusion treatment may reduce mortality in patients with severe sepsis and septic shock in specific disease severity subgroups.