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 pO2 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.