Asthma is a chronic multifactorial disease with frequent exacerbations in many patients. Much effort has been made to determine prevalent factors associated with difficult- to-control asthma. Here we report the case of a 57-year-old man who was treated for asthma during the last 4 years at our pulmonology clinic. Recently, the patient experienced severe dyspnea for more than 3 months despite the addition of the leukotriene modifier, theophylline and oral cortic-osteroid. Chest CT scans revealed multifocal areas of pulmonary arterial thrombosis. Doppler ultrasonograms showed multiple deep vein thrombi. The patient was diagnosed of having protein S deficiency and was treated with low molecular weight heparin, followed by oral warfarin. Now, he has no pulmonary arterial thrombosis and has no more asthmatic attack for half a year.