To examine associations of pulmonary artery catheter (PAC) use with in-hospital death and hospital length of stay (days) overall and within subgroups of hospitalized cardiac surgery patients. Secondary analyses of 1999–2019 National Inpatient Sample data were performed using 969,034 records (68% male, mean age: 65 years) representing adult cardiac surgery patients in the United States. A subgroup of 323,929 records corresponded to patients with congestive heart failure, pulmonary hypertension, mitral/tricuspid valve disease and/or combined surgeries. We evaluated PAC in relation to clinical outcomes using regression and targeted maximum likelihood estimation (TMLE). Hospitalized cardiac surgery patients experienced more in-hospital deaths and longer stays if they had ≥ 1 subgroup characteristics. For risk-adjusted models, in-hospital deaths were similar among recipients and non-recipients of PAC (odds ratio [OR] 1.04, 95% confidence interval [CI] 0.96, 1.12), although PAC was associated with more in-hospital deaths among the subgroup with congestive heart failure (OR 1.14, 95% CI 1.03, 1.26). PAC recipients experienced shorter stays than non-recipients (β =  − 0.40, 95% CI − 0.64, − 0.15), with variations by subgroup. We obtained comparable results using TMLE. In this retrospective cohort study, PAC was associated with shorter stays and similar in-hospital death rates among cardiac surgery patients. Worse clinical outcomes associated with PAC were observed only among patients with congestive heart failure. Prospective cohort studies and randomized controlled trials are needed to confirm and extend these preliminary findings.