To evaluate the beneficial effects of high-flow nasal cannula (HFNC) oxygen therapy during cesarean section in pregnant women with heart disease. We conducted a single-center, single-blinded randomized trial of HFNC oxygen therapy in pregnant women with heart disease undergoing cesarean section under neuraxial anesthesia.The participants were randomly assigned to receive either HFNC oxygen therapy with inspiratory flow of 30 L/min with 40% FIO2(n=27) or conventional oxygen therapy (COT) with oxygen flow rate of 5 L/min via a nasal cannula (n=31).The primary outcome was maternal desaturation (SpO2 < 94% lasting more than 3 min or PaO2/FIO2≤300 mmHg). Maternal desaturation was observed in 7.4%(2/27) of the women in HFNC group and in 32.3%(10/31) in the COT group.None of the cases required tracheal intubation during the perioperative period.The HFNC group had a significantly higher incidence of postoperative leukocytosis (P < 0.05) but without pyrexia or other inflammation-related symptoms.There were no significant differences between the two groups in the secondary maternal outcomes (need for respiratory support, maternal ICU admission, postoperative respiratory complications, and cardiovascular complications) or neonatal outcomes (P>0.05). In pregnant women with heart disease, HFNC therapy can significantly reduce the rate of maternal desaturation during the perioperative period of cesarean section without adverse effects on short-term maternal or fetal outcomes.