OBJECTIVES:  Air leaks after thoracic surgery are common, and can be associated with an increased risk of clinical complications and a significant economic burden, including increased length of stay and hospital resources. PROGEL™ Pleural Air Leak Sealant (PROGEL™) is the only FDA-approved sealant to treat intra-operative air leaks. The analyses presented here estimate healthcare utilization, medical costs, and outcomes in patients treated with PROGEL™ as compared to those outcomes associated with the use of other synthetic sealants or fibrin sealants. METHODS:  This was a retrospective analysis of both open and thoracoscopic lung resections including: lobectomy, bilobectomy, segmentectomy, decortication procedures, and wedge resections from the Premier Hospital Database, evaluating the clinical and economic outcomes of patients whose discharge data included ICD-9 codes for these procedures in the inpatient setting. Patients were analyzed using propensity score matching (PSM) to compare the use of PROGEL™ with other sealants (synthetic and fibrin). Adult patients (18 and older) with a hospitalization discharge between January 2009 and June 2015 were evaluated. Total costs, length of stay, readmissions, and clinical complications were collected. RESULTS:  PSM produced cohorts of 3,988 for PROGEL™, and 3,639 for other sealants. Utilization of PROGEL™ was associated with an adjusted all-cause mean cost savings of $4,062 as compared with other synthetic and fibrin sealants; $31,795 versus $35,858, p<0.001. PROGEL™ was also associated with an adjusted mean length of stay reduction of 1.35 days as compared with other synthetic and fibrin sealants (9.8 versus 11.2 days, p<0.001), and reduced risk of moderate or low infection. CONCLUSIONS:  After controlling for patient characteristics, risk factors, and comorbidities, as well as hospital characteristics and surgical procedures, a statistically significant lower healthcare utilization and hospital cost was found to be associated with the use of PROGEL™ compared to the use of other synthetic or fibrin sealants.