<b><i>Introduction:</i></b> Polymyxin B-immobilized fiber column direct hemoperfusion (PMX-DHP) is used for patients with septic shock, and the recommended hemoperfusion period is 2 h. However, it remains unclear whether the optimal duration is 2 h or longer. The purpose of this study was to compare the effects of PMX-DHP between conventional and longer duration of PMX-DHP. <b><i>Methods:</i></b> We retrospectively investigated 103 patients with sepsis who underwent PMX-DHP. The demographic data, routine biochemistry, microbiological data, and primary infection site were reviewed in the medical chart. The acute physiology and chronic health evaluation (APACHE) II score, sequential organ failure assessment (SOFA) score, heart rate, mean arterial pressure (MAP), vasoactive-inotropic score (VIS), and PaO<sub>2</sub>/FiO<sub>2</sub>, at baseline and day 3, were compared between the standard group (2 h of PMX-DHP) and the extended group (>2 h of PMX-DHP). <b><i>Results:</i></b> Median MAP was significantly lower and median VIS was significantly higher in the extended group at baseline (<i>p</i> < 0.05, 0.01, respectively) There were no significant differences in APACHE II score, SOFA score, and PaO<sub>2</sub>/FiO<sub>2</sub> at baseline between the 2 groups. The increase of MAP and the decrease in VIS from baseline to day 3 were significantly greater in the extended group (<i>p</i> < 0.01, respectively). In the extended group, increase in PaO<sub>2</sub>/FiO<sub>2</sub> was significantly larger in the patients who underwent ≥8 h duration than that in patients who underwent <8 h duration (<i>p</i> < 0.01). The ventilator-free days, the incidence of continuous renal replacement therapy, and the 28-day mortality were not different between the groups. <b><i>Discussion/Conclusions:</i></b> Longer duration of PMX-DHP was associated with the improved MAP and decreased volume of vasoactive-inotropic agents compared with the conventional duration. Eight and longer hours duration of PMX-DHP was associated with the improvement in the pulmonary oxygenation. Further studies are needed to confirm the efficacy of longer duration of PMX-DHP in patients with septic shock.