Percutaneous patent foramen ovale (PFO) occluder placement improves dyspnea and oxygen requirement in hypoxic patients with PFO-mediated right-to-left shunt (RTLS). Although saline contrast echocardiography (SCE) in the resting state can identify PFO RTLS, SCE performed with exercise stress testing may provide incremental diagnostic yield compared to rest SCE. We evaluated the ability of exercise SCE to predict PFO presence and size using intracardiac echocardiography (ICE) as a gold standard in a hypoxic cohort. Thirty-three hypoxic patients with suspected PFO RTLS who underwent rest, Valsalva, and exercise stress SCE prior to ICE were evaluated retrospectively. PFO RTLS was defined by ICE findings including PFO anatomy, RTLS by saline contrast and color Doppler, and probe patency. SCE shunt severity was compared to the presence of ICE-defined PFO RTLS and PFO size. Exercise SCE for the detection of PFO RTLS performed with an area under the curve of 0.77, sensitivity of 73 %, and specificity of 86 %. Among 26 patients with PFO RTLS, exercise SCE identified four additional patients with PFO that had negative rest SCE and two patients with negative Valsalva SCE. Exercise SCE had a stronger correlation with PFO size than resting or Valsalva SCE. Exercise SCE detects PFO RTLS and predicts PFO size in a hypoxic cohort. In addition, exercise SCE can identify PFO RTLS that is otherwise undetected with rest or Valsalva SCE. Exercise SCE may be appropriate when a clinical suspicion for PFO RTLS persists despite negative rest and Valsalva SCE.