OBJECTIVES This study aimed to compare vacuum-assisted closure therapy (VAC) and closed irrigation drainage therapy (CID) for deep sternal wound infection treatment in infants. METHODS From January 2008 to March 2018, 69 patients (1.73%) had deep sternal wound infection. They were divided into 2 groups: patients treated with VAC therapy (VAC group, 29 patients) and those treated with CID therapy (CID group, 40 patients). After performing a propensity score analysis (1:1) for the entire sample, 16 patients receiving VAC therapy were matched with 16 patients receiving CID therapy. RESULTS No significant difference was noted between both groups regarding age [d = 0.045; 95% confidence interval (CI) 0.99–1.07], gender (d = 0.001; 95% CI 0.22–4.45), weight (d = 0.011; 95% CI 0.73–1.35), body surface area (d = −0.023; 95% CI 0.01–5733.08), cardiopulmonary bypass (d = 0; 95% CI 0.16–5.90) and open chest duration (d = −0.112; 95% CI 0.31–5.16). Five patients died in the CID group (31.25%) during hospital stay, and there were no deaths in the VAC group (P = 0.024). Recurrence of mediastinitis occurred in 1 patient (6.25%) from the VAC group and in 6 patients (37.5%) from the CID group (P = 0.037). The multivariable regression analysis revealed that the CID method was the only risk factor for remediastinitis (odds ratio 17.3; 95% CI 1.04–286.75; P = 0.046). CONCLUSIONS Use of VAC therapy in infants with deep sternal wound infection was associated with a substantial decrease in the mortality rate and duration of therapy compared with CID technique. The CID technique was an independent risk factor for recurrence of mediastinitis.