The premise of this retrospective study was to evaluate the intraoperative use of closed-incision negative pressure therapy (ciNPT) to help reduce the incidence of postoperative sternal wound infections in multimorbid patients with an elevated risk of developing a sternal wound infection post cardiac surgery versus a cohort that received standard-of-care dressings. Data for all adult patients were collected from each cardiothoracic surgery unit across 3 hospitals in the United Kingdom. High-risk patients had 2 or more recognized risk factors. Fisher's exact test (two-tailed) and unpaired t-test were used to help analyse categorical and continuous data. Propensity matching was performed to compare the 2 groups. A total of 5,288 patients who had cardiac surgery were included. Propensity matching led to 766 matched cases. There were significantly fewer sternal wound infections in the ciNPT group [43 (5.6%) vs 119 (15.5%) cases; P = 0.0001], as well as fewer deep sternal wound infections [14 (1.8%) vs 31 (4.0%) cases; P = 0.0149] and superficial sternal wound infections [29 (3.8%) vs 88 (11.4%) cases; P = 0.0001]. A higher mean length of stay in the ciNPT group was statistically significant (11.23 ± 13 vs 9.66 ± 10 days; P = 0.0083) as was a significantly higher mean logistic European System for Cardiac Operative Risk Evaluation (EuroSCORE) (11.143 ± 13 vs 8.094 ± 11; P = 0.0001). A statistically significant higher readmission to the intensive care unit due to sternal wound infection was noted for the controls [16 (2.08%) vs 3 (0.39%) readmissions; P = 0.0042]. The ciNPT appears to be an effective intervention to help reduce the incidence of sternal wound infection in high-risk individuals undergoing cardiac surgery.