BACKGROUND: Pulmonary vascular bed volume (PVBV) in cryptogenic stroke patients with patent foramen ovale (PFO) has not been well characterized. This study examined PVBV in cryptogenic stroke patients with suspected PFO. METHODS: A total of 469 patients underwent agitated saline contrast transthoracic echocardiography (TTE) and transesophageal echocardiography (TEE) between January 2021 and December 2024. PVBV was quantified by myocardial contrast echocardiography (MCE). RESULTS: Of the included patients, 423 were diagnosed with PFO, and 46 served as controls. The PFO group demonstrated elevated pulmonary vascular resistance (PVR) and reduced right ventricular systolic function (all P<0.05), with significantly reduced PVBV compared to controls [242.89 (202.91-465.05) . 465.19 (422.53-536.35) mL, P<0.0001]. Multivariate analysis identified right-to-left shunt (RLS) severity, body surface area (BSA), and male gender as independent predictors of PVBV (P<0.05), modeled by the equation: PVBV = 623.427 × BSA - 39.559 × right-to-left shunt level - 130.929 × gender (male =1) - 622.993 (R=0.447, P<0.0001). The model effectively predicted PVBV below 250 mL, with an area under the receiver operating characteristic curve (AUC) of 0.811 (sensitivity, 77.2%; specificity, 86.2%). For PVBV below 200 mL, the AUC improved to 0.881 (sensitivity, 100%; specificity, 73.9%). CONCLUSIONS: PVBV is reduced in cryptogenic stroke patients with PFO, and right-to-left shunt level, BSA, and gender were the factors associated with PVBV. Addressing these gaps could enhance the understanding of cardiopulmonary interactions in PFO.