Background: Remote patient monitoring (RPM) may improve the early detection and mitigation of cancer treatment-related complications, health-related outcomes and quality of life. RPM’s success may depend, in part, on patients’ adherence to remote monitoring protocols. However, factors that influence adherence to RPM are largely unknown. Daily blood pressure/pulse (BP/P), weight, and electronic patient-reported outcomes (ePROs) were monitored remotely in head and neck cancer (HNC) patients undergoing radiation treatment (RT) to identify dehydration risk. We evaluated potential factors associated with RPM adherence. Methods: During RT (average 6 to 7 weeks), participants were asked to take daily (Monday-Friday) measures of BP/P and weight using Bluetooth-enabled devices and to complete daily ePROs using a mobile tablet application (app). Data were provided to their physicians for daily review. The MD Anderson Symptom Inventory-Head and Neck (MDASI-HN) was completed at baseline and end of RT, and 6-8 weeks post-RT completion. The Patient Activation Measure (PAM) was completed at baseline and 6-8 weeks post-RT completion. A device usability survey measuring perceived usefulness of RPM was completed at the end of RT. Adherence to daily monitoring was recorded objectively. Longitudinal analyses compared the relationship between demographic, clinical, and PRO data and monitoring adherence. Results: Participants (n = 169) were 80% male, 87% White, and 91% married. Overall adherence to monitoring BP/P, weight, and ePROs was 83%, 82% and 74%, respectively. Greater HN-specific symptom severity and interference was associated with decreased adherence to daily monitoring of BP/P, weight, and ePROs (P< 0.021). Higher PAM scores were associated with higher adherence to daily monitoring of BP/P only (p = 0.006). Participants reported modest levels of perceived usefulness of RPM across four categories: symptom management, early problem detection, illness monitoring by healthcare provider, and feeling of security during RT. Only a single item indicating perceived feeling of security was associated with greater adherence to daily monitoring of blood pressure/pulse (p = 0.032) and weight (p = 0.007). Conclusions: A benefit of frequent RPM may be early detection and mitigation of symptoms during RT for HNC, however, increasing symptom burden experienced during treatment may interfere with adherence to daily monitoring. Better adherence may be attributed to patients perceiving a sense of security from daily monitoring and may suggest a potentially important value that patients gain from RPM. Understanding factors that impact patient adherence to RPM may help improve acceptability and clinical utility of RPM in oncology. Clinical trial information: NCT02253238.