Background: Smart phone web based applications (apps) can be effective communication tools for monitoring compliance and increasing adherence to oral anti-cancer therapy in the outpatient setting. Methods: Cancer patients age 18-90 treated with various oral anti-cancer therapies were recruited to this prospective, 3 month observational trial at our large community cancer center to determine feasibility of using an app for oral anti-cancer therapy compliance. Enrolled patients are randomized to either Arm 1 App arm and nurse counseling or Arm 2 nurse counseling only. The free apps MyMeds and Medisafe incorporate medication reminders and record doses. Patients complete the validated RAND 36- item quality of life (QOL) questionnaire and a free text feedback. Results: 91 patients were screened between 11/2015 to 9/2016 (45 declined enrollment due to various factors). 46 patients were randomized with 25 to Arm 1 and 21 to Arm 2. Demographics included 10 men (various tumor types but mostly multiple myeloma) and 36 women; 22 with breast cancer. MyMeds app lacked the necessary real-time communication so patients were switched to the MediSafe app which features email alerts. 15 patients have completed the study through Month 3. Four patients on Arm 1 missing their monthly visit or were non-compliant with the app. 23 patients remain active in the study. Differences are a higher QOL score in Arm 1 vs Arm 2 in measured domains of Energy/Fatigue (56% in Arm 1 compared to 44% for Arm 2) and Pain (72% in Arm 1 compared to 58% in Arm 2). Patients randomized to the app found the electronic alerts very helpful. Conclusions: Our limited pilot study demonstrated the potential of smart device apps as effective communication tools for improving patients’ adherence to oral anti-cancer therapy and QOL. Ultimately, convenient ways to monitor patients’ compliance with anti-cancer therapy will impact survival and facilitate provider-patient communication.