Objective: Cardiopulmonary bypass (CPB) elicts an inflammatory response which is potentially harmful and that is partly caused by activation of leukocytes. Despite promise from earlier studies, however, the value of intraoperative leukocyte-depletion (LD) remains equivocal. We studied the effect of LD during routine cardiac surgery. Methods: For a short period (2.5 months), all operations at our institution were performed with leukocyte filters (Pall, East Hills, NY, USA) in the arterial and cardioplegia lines of the CPB. Those patients operated immediately before and after this period served as controls. Results: In each group, 266 predominantly male (70%) patients were studied. A broad spectrum of operations including emergency surgery was evaluated, which was comparable between the groups (P=0.41). There were no significant differences regarding the preoperative data, but the preoperative leukocyte count tended to be lower in the leukodepletion-group (7961±2415 vs. 8444±2951, P=0.050). Despite this, no difference between the groups regarding the postoperative leukocyte count was observed. Significantly more LD-patients were extubated within 12 h postoperatively (69% vs. 60% in the controlgroup, P=0.029), but there were no significant differences regarding 30-day mortality (0.4% vs. 1.1%, P=0.37), transfusion requirements or major morbidity. Conclusions: In a retrospective study on adding LD filters to all cardiac operations with CPB in adults, we did not observe a clear benefit of intraoperative LD with the strategy used (continuous filtration plus filtration of cardioplegia).