Objectives This study evaluated the safety and efficacy of a cosmetic right lateral thoracotomy for ventricular septal defect (VSD) repair in infants weighing less than 5 kg. Methods Eighty-nine infants who underwent a right lateral thoracotomy (right group) and 116 infants who underwent a median sternotomy (median group) were included. Patient characteristics, and perioperative and follow-up data were retrospectively analysed. Results Patient characteristics were comparable between the two groups as were cardiopulmonary bypass and aortic cross-clamping time, length of intensive care unit stay, ventilation duration and application of inotropic drugs. Compared to the median group, there was shorter procedure time (p < 0.05), shorter length of incision (p < 0.05), and less drainage and transfusion in the right group (p < 0.05). The peak airway pressure, partial oxygen pressure, partial carbon dioxide pressure, oxygenation index and alveolar-arterial oxygen gradients were similar for these two groups at the four time points analysed. No deaths occurred in either group and differences in morbidity were insignificant. No cardiac or thoracotomy-related complications occurred within the 18.4 +/- 9.9 month follow-up. Conclusions A right lateral thoracotomy reduces operative traumas and is as safe and effective as a median sternotomy at VSD repair in infants under 5 kg in weight.