OBJECTIVES: For patients with uncontrolled hypertension, differentiation of pharmacological resistance from inadequate or improper medication use is key to clinical management. Proteus Digital Health has developed a unique digital feedback system, which utilizes an Ingestible Sensor (IS) to determine medication-taking patterns. A wearable sensor in the form of an adhesive patch collects timing and taking of IS ingestions, and physiological and behavioral metrics such as heart rate, and patterns of activity and rest, providing insights into the patient’s day-to-day lifestyle. This study evaluates the utility of the Proteus system in patients with uncontrolled hypertension. METHODS: Patients with a history of uncontrolled hypertension (BP>140/90) at 5 primary care centers in the United Kingdom were prescribed the Proteus system for 14 days. Patients co-ingested the IS along with their prescribed BP medications while simultaneously wearing the patch.  BP was measured on days 1 and 14 by a clinician, and all other parameters, such as adherence, activity and rest patterns, were collected via the Proteus system.   RESULTS: Of the 190 patients, 21 patients had incomplete data.  In the remaining 169 patients (89%), mean medication adherence was 88%, and mean BP decrease was -7.6 mm Hg systolic and -3.8 mm Hg diastolic.  The system data provided diagnostic insight differentiating non-response vs. non-adherence. One hundred forty-eight (78%) patients had ≥70% adherence; 100 (53%) achieved blood pressure control on their prescribed therapy, and 48 (25%) remained uncontrolled and required modification of their therapeutic regimen.  The remaining 21 patients (11%) were identified as needing intervention to support medication adherence. CONCLUSIONS: In patients with a history of uncontrolled hypertension, 53% achieved BP control within 2 weeks, and 25% received an informed therapeutic intervention using the Proteus system.  Thus, Proteus can identify specific individual needs for progressing through the recommended treatment pathway and for advancing toward treatment goals.