The biatrial approach has been the classic means of access for left atrial myxoma resection. Increased surgical experience led cardiac surgeons to favour the uniatrial approach to reduce incisions and achieve adequate exposure. In this study, two unilateral surgical approaches were compared in 18 consecutive left atrial myxoma cases. Patients were divided into two groups according to the surgical approach: left atriotomy (group 1, n = 9) and right atriotomy trans-septal approach (group 2, n = 9). Comparison criteria included pre- and post-operative functional capacity, cardiac rhythm, left ventricular ejection fraction, pulmonary artery pressure, left atrial dimensions, cardiopulmonary bypass time, aortic cross-clamp time, drainage over 48 h post-operatively, units of blood transfused, extubation time and length of stay in the intensive care unit and hospital. No significant between-group difference was observed in any criteria except aortic cross-clamp time, which was significantly longer in group 2 than in group 1. No recurrence of myxoma occurred in either group for the 15 patients followed up. Right atrial trans-septal incision appears to be as safe and effective as the left atriotomy approach for left atrial myxoma resection.