To investigate procalcitonin (PCT) levels in patients undergoing cardiopulmonary bypass (CPB) in order to assess the prevalence and prognostic capacity of elevated PCT levels following CPB in open heart surgery. prospective observational study in consecutive patients. Twenty-four-bed ICU, department of thoracic and cardiovascular surgery, university hospital. Seven hundred and twenty two patients, 691 of whom underwent CPB, i.e., 476 had coronary bypass surgery (CABG), 130 valve replacement, 34 combined CABG and valve replacement and 23 thoracic aortic surgery. Standard perfusion techniques were used with cardioplegic arrest and mild hypothermia (28–32°C). With the exception of thoracic aortic procedures, full-flow perfusion was performed. PCT was measured prior to surgery and daily thereafter until ICU discharge or death. PCT significantly increased at day 1 postoperatively compared to baseline values (0.25±1.65 vs 6.49±22.0 ng/ml, p<0.005). However, in 55.1% of patients PCT was below 1.0 ng/ml. In 12.8% of CABG patients PCT was increased to >5.0 ng/ml, compared to 39% in valve patients and 35% of patients with aortic surgery. An elevated PCT level >1.0–5.0 ng/ml at day 1 was highly predictive of mortality (P<0.03, vs<1.0 ng/ml), with an additional accuracy when levels >5.0 ng/ml were measured (P<0.002 vs<1.0 ng/ml). These results provide evidence that PCT might serve as an early prognostic marker in patients undergoing CPB in open heart surgery. It may be worth considering immunomodulating approaches in patients presenting elevated PCT levels in the early phase after CPB.