Objective To explore the impact of combined oral-nasal cavity and skin decolonization on postoperative pulmonary infection in heart transplant patients. Methods A total of 85 patients who underwent heart transplant surgery at the First Affiliated Hospital of Xi’an Jiaotong University from September 2023 to October 2025 were selected as the study subjects. They were randomly divided into an intervention group (n=42) and a control group (n=43) using a random number table method. The control group received routine nursing measures, while the intervention group received combined oral-nasal cavity and skin decolonization intervention. The incidence of pulmonary infection, laboratory test results, duration of mechanical ventilation, and intensive care unit (ICU) stay between two groups of patients were compared. Patients underwent a 3-month follow-up after surgery to compare pulmonary infection and survival status. Results The incidence of pulmonary infection in intervention group was 23.8% (10/42), which was lower than 44.2% (19/43) of control group, and difference was statistically significant (P=0.048). In terms of infection types, patients in the intervention group were mainly infected with single bacteria (80.0%), while those in the control group were mostly infected with mixed bacteria (68.4%), with statistically significant diffe-rence (P=0.021). In terms of pathogen distribution, for patients in the control group, Gram-positive bacteria (mainly Staphylococcus aureus) infection accounted for 52.6%, while the intervention group was predominantly infected with Gram-negative bacteria (90.0%), with Gram-positive bacteria accounting for only 10.0%. Difference between the two groups was statistically significant (P=0.044). In terms of laboratory indicators, there were no statistically significant differences in white blood cell count, absolute neutrophil count, lymphocyte count, and C-reactive protein level between the two groups of patients before the initial intervention (all P>0.05). After 5 days of continuous intervention and 5 days after the end of the intervention, the white blood cell count, absolute neutrophil count, and C-reactive protein level in patients in the intervention group were all lower than those in the control group (all P<0.05), while the lymphocyte count was higher than that in the control group (all P<0.05). The duration of mechanical ventilation and ICU stay in patients in the intervention group were both shorter than those in the control group (both P<0.05). The 3-month follow-up results showed that the incidence of pulmonary infection in patients in the intervention group was 11.9% (5/42), which was lower than 32.6% (14/43) in the control group, and the difference was statistically significant (P=0.022). There was no statistically significant difference in survival rate between the two groups of patients (P=0.676). Conclusion Combined oral-nasal cavity and skin decolonization can reduce the incidence of postoperative pulmonary infection in heart transplant patients, decrease mixed infection, as well as shorten duration of mechanical ventilation and length of ICU stay in heart transplant patients.