Cardiac surgery with cardiopulmonary bypass (CPB) frequently leads to systemic inflammatory response syndrome (SIRS) with concomitant organ malfunction. Infused particles may exacerbate inflammatory syndromes since they activate the coagulation cascade and alter inflammatory response or microvascular perfusion. In a randomized, controlled, prospective trial, we have previously shown that particle-retentive in-line filtration prevented major complications in critically ill children. Now, we investigated the effect of in-line filtration on major complications in the subgroup of cardiac patients. Children admitted to tertiary pediatric intensive care unit were randomized to either control or filter group obtaining in-line filtration throughout complete infusion therapy. Risk differences and 95 % confidence intervals (CI) of several complications such as SIRS, sepsis, mortality, various organ failure and dysfunction were compared between both groups using the Wald method. 305 children (n = 150 control, n = 155 filter group) with cardiac diseases were finally analyzed. The majority was admitted after cardiac surgery with CPB. Risk of SIRS to -0.5 %), renal (-10.0 %; 95 % CI -17.0 to -3.0 %) and hematologic (-8.1 %; 95 % CI -14.2 to -0.2 %) dysfunction were significantly decreased within the filter group. No risk differences were demonstrated for occurrence of sepsis, any other organ failure or dysfunctions between both groups. Infused particles might aggravate a systemic hypercoagulability and inflammation with subsequent organ malfunction in pediatric cardiac intensive care patients. Particle-retentive in-line filtration might be effective in preventing SIRS and maintaining renal and hematologic function. In-line filtration offers a novel therapeutic option to decrease morbidity in cardiac intensive care.