Background: The differences in colorectal cancer (CRC) treatment between infusion and oral chemotherapy have challenged clinical teams to maintain clinical quality and patient communications with self-administered therapies. The complexity of many regimens, such as capecitabine, creates challenges with dosing and adverse event (AE) management. The first novel Digital Medicine Program (DMP), aimed at providing support to patients and providers, was integrated into CRC treatment at Fairview Health Services and University of Minnesota Health. The DMP consists of DigiMeds (medications co-encapsulated with ingestible sensors), a wearable patch, and a mobile app to facilitate passive collection of actual medication ingestion data and biometrics over time. Methods: Beginning in September 2018, patients with CRC were offered the DMP to augment standard of care. Clinical pharmacists monitored medication adherence and biometrics in near real-time through a secure web portal. This data was used to address barriers to adherence and adjust therapy when appropriate. Qualitative data regarding provider experiences with the DMP and their interactions with patients were collected via a 5-question survey. Results: Eleven patients used the DMP (age: 66.9 ± 9.9 years (mean ± SD); patch wear: 89.9 ± 11.6%; average adherence: 91.0 ± 5.6%) for 140 ± 137 days. Providers reported that the DMP enabled data-driven decision-making by helping identify non-adherence, prompted timely dose modification for AE management, and allowed personalized care and targeted counseling. Integration of the DMP data into the Electronic Medical Record system improved utility, but providers called the DMP a “time-saver”, creating a “proactive rather than reactive” care process in “ways no other technology can do”. Providers stated patients felt more ownership of their care, and that DMP revealed newly “quantifiable positive changes” in their cancer care. Conclusions: Use of the DMP in this small cohort enabled proactive decision-making and facilitated patient-focused and efficient care. Future pragmatic, large real-world studies are underway to assess the impact of DMP on adherence, AE management, and clinical and economic outcomes.