Introduction: Postoperative cognitive dysfunction (POCD) generally characterized as impairment in attention, cognition, recognition, orientation, memory and learning, is more evident after cardiac rather than non-cardiac surgery. The use of extracorporeal circulation (ECC) in heart surgery enhances this phenomenon. The recently introduced in the clinical practice mini-extracorporeal circulation (MECC) systems were challenged whether they may attenuate the outcome as compared with the conventional extracorporeal circulation (CECC). Patients and methods:We examined 60 patients who underwent coronary artery bypass grafting on either of the two systems of ECC (Group A - MECC: 29 patients and Group B - CECC: 31 patients) with a series of neuropsychological tests before surgery, prior to discharge and at 3-month follow-up. The assessment included measures of attention and concentration, verbal working memory, executive functioning, learning, short-term and long-term memory, visuospatial perception, speed of information processing, anxiety and depression. Results: Despite the similar preoperative performance of both groups, patients who underwent surgery on MECC outperformed those being operated on CECC systems on most of the neuropsychological domains at follow-up: executive functioning, attention and visual tracking, verbal working memory, short-term and long-term memory and visuospatial perception. In particular, MECC group showed better performance on executive functioning and inhibition of a learned response (p=0.04), attention and complex scanning (p=0.000) and verbal working memory (p=.008). MECC patients also performed better than CECC patients on short-term memory (p=0.001), long-term-memory (p=0.000) and visuospatial perception (p=0.04). Moreover, the follow-up performance of the MECC group of patients exceeded their preoperative neurocognitive levels suggesting less overall postoperative cognitive dysfunction in these patients. In contrast, the CECC group showed cognitive decline on most of the neuropsychological domains immediately and 3 months after surgery, without those patients being able to reach their preoperative neurocognitive levels. Conclusion: Given the frequency and severity of POCD after heart surgery and its impact on patients’ performance and quality of life, our findings suggest that use of MECC systems may be beneficial for the neurocognitive outcome of the patients. This may be of particular importance for the choice of the surgical management of the patients undergoing heart surgery.