Objective: To investigate the efficacy of dornase alpha, a mucolytic agent, in children who developed pulmonary atelectasis after congenital heart surgery. Design: Retrospective case-control study. Setting: Paediatric cardiac intensive care unit at a tertiary care hospital. Patients: Between July, 2011 and July, 2012, 41 patients who underwent congenital cardiac operations and developed post-operative pulmonary atelectasis that was resistant to conventional treatment and chest physiotherapy. Interventions: In all, 26 patients received dornase alpha treatment. As a control group, 15 patients were treated with conventional medications and chest physiotherapy. Main results: The median age of patients was 25.5 (3-480) days in the study group and 50.0 (3-480) days in the control group. A total of 15 (57.6%) patients in the study group and 8 (53.3%) patients in the control group were male. The median weight was 4.2 (2.9-14.2) kg and 4.0 (3.5-13.6) kg in the study and control group, respectively. In the study group, pulmonary atelectasis was diagnosed at a median period of 5 (2-18) days after operations, whereas in the control group atelectasis was diagnosed at a median period of post-operative 6 (3-19) days. In the study group, the median atelectasis score decreased from 3.4 (1-6) to 0.8 (0-3) (p = 0.001). The median pO(2) level increased from 69 (17-142) mmHg to 89 (30-168) mmHg (p = 0.04). In addition, heart rate and respiratory rate per minute were significantly decreased (p < 0.05). There were no significant changes in these parameters in the control group. Conclusions: The use of dornase alpha can be effective for the management of pulmonary atelectasis that develops following congenital heart surgery.