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A high incidence of postoperative pulmonary complications (PPCs) occurs in elderly patients due to general anesthesia. Studies show lower ventilation driving pressures may result in fewer PPCs. Appropriate levels of positive end-expiratory pressure (PEEP) may also help prevent developing PPCs in patients undergoing general anesthesia. This study aimed to test the hypothesis that driving pressure-guided PEEP titration ventilation could effectively reduce the incidence of PPCs, optimize respiratory mechanics, and improve lung oxygenation during mechanical ventilation in elderly patients undergoing laparoscopic colorectal cancer surgery. This randomized, parallel group, patient- and outcome assessor-blinded, single-center trial included a total of 70 elderly patients scheduled for laparoscopic colorectal cancer surgery. Patients were randomly divided into two groups: the titration group (receiving driving pressure-guided PEEP titration ventilation) and the control group (receiving a fixed PEEP of 5 cmH2O). The primary endpoint was the incidence of PPCs ≥moderate severity within 7 days after surgery. The secondary endpoints included pulmonary oxygenation and respiratory mechanics values during surgery, post-anesthesia care unit (PACU) discharge times, and length of hospital stay. The incidence of PPCs ≥moderate severity within 7 days after surgery was significantly lower in the titration group (17.1%) than in the control group (45.7%) (Relative Risk (RR), 0.375; 95% Confidence Interval (CI), 0.166 to 0.845; p = 0.010). The titration group demonstrated higher dynamic lung compliance and oxygenation during mechanical ventilation than the control group. PACU discharge times and length of hospital stay were similar in both groups (p > 0.05). In elderly patients undergoing laparoscopic colorectal cancer surgery, driving pressure-guided PEEP titration ventilation significantly reduced the incidence of PPCs and increased dynamic lung compliance and oxygenation. [ABSTRACT FROM AUTHOR]