Acute pulmonary embolism is one of the common manifestations of hereditary protein S deficiency. We present a 48-year-old woman suffering from acute dyspnea after orthopedic surgery on her right lower leg. She had hereditary protein S deficiency and acute pulmonary embolism (APE). Additionally, atrial septal defect(ASD) was disclosed in the diagnostic process. After heparin use, her condition improved. She underwent surgical correction of ASD several months later uneventfully.