Warfarin, an anticoagulant with high risk on the fatal adverse effects, the safety monitoring system in primary health care is needed for patients in the community.  This study aimed to investigate problems of warfarin use, to discover factors related to the blood clotting, and to develop a safety monitoring system for warfarin. A mixed method was conducted in two phases. Phase one consisted of home visit for 104 patients with warfarin which aimed to investigate use problems. Phase two; the focus groups included all stakeholders were done which aimed to develop a community-based system grounded on the Chronic Care Model (CCM). The warfarin monitoring system was implemented for a month and briefly evaluated the stakeholders’ satisfaction on it.  The results revealed that: Phase one, 38.5% patients with warfarin at home had missed their treatment appointments. Their warfarin compliance was 91.1+21.3%. 53.5% had unused warfarin at home; 37.4% had inappropriate warfarin storage; 13.1% suffered the side effect of minor bleeding; 17.3% potentially had warfarin-herb interactions; 61.3% experienced drug-warfarin interaction. Two factors significantly affecting on the International Normalized Ratio (INR) and %Time in Therapeutic Range (%TTR) were inappropriate warfarin dosages and taking other medications. %TTR was influenced by warfarin compliance. Stage two, the safety monitoring system and protocol were created using CCM. The developed system composed of six elements that were joint operation of primary health care personnel and inter-professional team of the hospital. This promoted the continuity of services from hospital to community.  After one-month implementation by an inter-professional team, all three groups of stakeholders were satisfied with its results. We concluded that the main problem afflicting warfarin patients was missed treatment appointments. Receiving extra medicines from other services, inappropriate dosage, and non-compliance. The developed warfarin monitoring system covered patients in primary health care, and all stakeholders were satisfied on its outcomes.