Objective: To investigate the feasibility of using a wireless wearable device (WD) in differentiated thyroid cancer (DTC) patients undergoing radionuclide therapy with I-131 (RAI) and protected hospitalization, this study compared the measurements of residual radioactivity obtained with those registered by a permanent environmental home device (HD). Methods: Twenty consecutive patients undergoing RAI hospitalized in restricted, controlled areas were enrolled. The patients underwent comprehensive monitoring of vital/nonvital parameters. We obtained 45580±113 measurements from the WD, detecting the residual radioactivity for each patient during approximately 56 hours of hospitalization, collecting data 53 times per hour. The samples, collected during daily activities, were averaged every two hours, and the results correlated with those from the HD. Bland-Altman analysis was also used to evaluate the agreement between the two techniques. Results: A significant relationship between the WD and HD was observed (r=0.96, p<0.0001). Bland-Altman analysis recognized the agreement between measurements by the WD and HD. The mean value at the end of the first day of hospitalization was 80.81 microSv/h and 60.77 microSv/h (p=ns for WD and HD), whereas those at the end of the second day were 47.08 and 24.96 (p=ns). In the generalized linear model (GLM), a similar trend in performance across time was found with the two techniques. Conclusions: This study demonstrates good agreement between the residual radioactivity measures estimated by the WD and HD modalities, rendering them interchangeable. This approach will allow both the optimization of medical staff exposure and safer patient discharge.