This study aimed to investigate the predictive effect of static lung compliance (SLC) and airway resistance (AR) in patients undergoing minimally invasive cardiac surgery (MICS) with unilateral pulmonary edema (UPE). A total of 245 patients who underwent MICS via cardiopulmonary bypass and minimal right lateral thoracic incision port access were enrolled, with immediate postoperative SLC and AR data collected upon intensive care unit (ICU) admission. Cutoff values for grouping patients into high (H-) and low (L-) compliance/resistance categories were determined using receiver-operating characteristic curves and Youden indexes. The primary outcome was the incidence of radiographically and clinically defined UPE within the first 24 hours postoperatively, while the secondary outcomes included duration of mechanical ventilation, length of ICU stay, total hospitalization days, in-hospital mortality, and the highest sequential organ failure assessment (SOFA) and acute physiology and chronic health evaluation II (APACHE-II) scores within the first 24 hours post-surgery. Results showed that patients in the L-compliance group (SLC <
40 mL/cmH2O) had longer durations of mechanical ventilation, length of ICU stay, and total hospitalization days, along with higher SOFA and APACHE-II scores compared to those in the H-compliance group (SLC ≥ 40 mL/cmH2O) (P <
.05), although there was no significant difference in in-hospital mortality. Conversely, patients in the H-resistance group (AR ≥ 11 cm H2O/[L·s]) exhibited longer durations of mechanical ventilation, length of ICU stay, and total hospitalization days, as well as significantly higher SOFA, APACHE-II scores, but lower in-hospital mortality rates than those in the L-resistance group (AR <
11 cm H2O/[L·s]) (P <
.05). In summary, immediate postoperative SLC <
40 mL/cm H2O and AR >
11 cm H2O/(L·s) are potentially valuable indicators for predicting postoperative UPE in patients undergoing MICS.