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Detecting warfarin levels in the blood is of critical importance in anticoagulant therapy because it is imperative that the concentration of the drug is maintained within a specific range. In this paper, we present a proof-of-concept of a novel sensing device based on ion-selective electrode (ISE) technology for the direct detection of warfarin in blood samples without any sample pretreatment. We used tetradodecylammonium chloride (TDDA) as an ion-exchanger to fabricate an ion-selective membrane. The ISE we developed showed high sensitivity, with a limit of detection (LOD) of 1.25 × 10⁻⁷ M and 1.4 × 10⁻⁵ M for detecting warfarin in buffer and blood, respectively. The sensor also exhibited promising selectivity in identifying the presence of various ions including chloride and salicylate, the most abundant ions in blood with a calibration slope of 58.8 mV/dec. We envision combining the ISE with a microfluidic system and a simple potentiometer to produce a sensitive, selective, and portable point-of-care testing device for monitoring the level of warfarin in patients’ blood during treatment.