Objective. The use of polymyxin B-immobilized fiber (PMX-F) treatment has been demonstrated to reduce chemical mediators of sepsis. The objective of the present study was to evaluate the effects of PMX-F treatment in patients with sepsis. Methods. The design of this study was prospective. Between January 1997 and April 2002, 314 patients were treated for severe sepsis or septic organ failure. Of these patients, 206 were treated by PMX-F hemoperfusion, during which standard supportive care was continued without alteration. The remaining 108 patients were treated by conventional means. Serum levels of mediators-including endotoxin, interleukin-6, tumor necrosis factor-a, soluble interleukin-2 receptor, endothelin-1, and platelet factor-4-were measured before and immediately after PMX-F treatment. Results. The post-treatment 2-week survival rate was 69% in the PMX-F treatment group and 36% in the conventional treatment group (p < 0.01). In the PMX-F treatment group, the sepsis severity score, the Goris score for the number of failed organs, and the Acute Physiology and Chronic Health Evaluation (APACHE) II score in survivors were significantly less than those in non-survivors (p < 0.01). In the survivors, all mediators were significantly decreased after PMX-F treatment (p < 0.01); however, there were no significant changes in the mediators in non-survivors. Conclusion. These data suggest that PMX-F hemoperfusion is superior to conventional treatment in patients with sepsis and is effective in reducing endotoxin and blood inflammation mediators in surviving septic patients.