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We designed this study to examine the clinical effects of polymyxin B hemoperfusion (PMX-HP) in septic shock patients.We retrospectively examined the effects of PMX-HP in septic shock patients with intra-abdominal or gram-negative bacterial infection during October 2013–May 2016. A one-to-one matching between the PMX-HP and conventional groups was performed, and 28-day mortality, and change in inotropic score, Sequential Organ Failure Assessment (SOFA) score, and Acute Physiology and Chronic Health Evaluation II (APACHE II) score at 24 h in the two groups were compared. In addition, multivariable regression analysis and Cox proportional hazards regression model were applied in all eligible patients.Sixty-nine patients were eligible, of whom fifty patients were enrolled for matched cohort analysis. In matched cohort analysis, change in inotropic score after 24 h (−24.8 [19.7] vs. −6.4 [20.0], p = 0.002) differed significantly between the PMX-HP and conventional groups. Multivariable regression analysis revealed that PMX-HP was associated with lower 28-day mortality (odds ratio 0.18, 95% CI 0.04–0.92, p = 0.039) and greater improvement in inotropic and APACHE II scores.PMX-HP may have potential benefits for hemodynamic and prognostic outcomes in septic shock patients with intra-abdominal or gram-negative bacterial infection.Polymyxin B hemoperfusion (PMX-HP) reduces endotoxin-induced inflammation.Discrepancies in the clinical benefits of PMX-HP exist in different studies.These discrepancies might result from different target population of patients.PMX-HP improved survival in septic shock patients with intra-abdominal infection.