Background: Failing heart has been described as the main mechanism of an unsuccessful separation the mechanical ventilator after cardiac surgery. Brain natriuretic peptide (BNP) is a specific marker for cardiac dysfunction. We aimed to evaluate the relationships between BNP levels and the duration of mechanical ventilation and the length of stay at the intensive care unit (ICU) after pediatric cardiac surgery. Methods: In this observational study, 52 infants aged between 2 and 50 months who underwent cardiac surgery were enrolled. Anesthesia and cardiopulmonary bypass methods were similar, and the weaning protocol in the ICU was the same in all the patients. The levels of pro-BNP and plasma lactate were recorded before surgery; at the time of ICU admission; and 24, 48, and 72 hours afterward. At the end of the study, the relationships between the levels of BNP and plasma lactate and the duration of mechanical ventilation and the length of stay at the ICU were assessed. Results: Of the 52 patients, 35 (67.3%) were male. The mean age and weight were 17.14±12.50 months and 9.01±2.98 kg, respectively. The mean duration of cardiopulmonary bypass was 191.25±34.15 minutes, and the mean aortic cross-clamp time was 75.48±31.88 minutes. The mean duration of mechanical ventilation was 21.78±18.78 minutes, and the mean length of stay at the ICU was 133.67±97.68 hours. The results showed that there was no significant relationship between the pro-BNP level and the duration of mechanical ventilation (P>0.05). The levels of pro-BNP at the time of ICU admission and 24 and 48 hours after surgery had a direct relationship with the duration of ICU stay (P<0.05). Conclusions: In the present study, higher serum pro-BNP levels at the time of ICU admission and 24 and 48 hours after admission were related to a prolonged ICU stay. However, the serum BNP level was not correlated with the duration of mechanical ventilation after pediatric cardiac surgery. (Iranian Heart Journal 2018; 19(4): 40-46)