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 corticosteroid. 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.