Purpose Patients receiving high-dose I-131 to treat differentiated thyroid cancer are isolated from visitors to limit radiation exposure to reasonable levels. The appropriate isolation time is unclear and has not been reported in Korea. The purpose of this study was to estimate the isolation time and investigate the possibility of earlier release from isolation. Methods This study was a retrospective analysis of data from 71 patients (10 men and 61 women; mean age, $49{pm}11.1;y$) who received 3.7 GBq (47 patients), 5.55 GBq (23 patients), or 7.4 GBq (1 patient) of I-131 between January 2008 and December 2008. The radiation dose was measured with a fixed probe placed inside the isolation room. The total estimated dose equivalent (TEDE) to family members, the time required for the external dose rate to become <0.07 mSv/h, and the time required for whole-body retention to become <1.2 GBq were calculated. Results By the TEDE criterion (<5 mSv), 70 of 71 patients (98.6%) could have been released without isolation. By the external dose rate criterion, 10 of 71 (14.1%) and 60 of 71 patients (84.5%) could have been released without isolation and within 24 h, respectively. With whole-body retention criterion, 19 of 71 (26.8%) and 48 of 71 patients (67.6%) could have been released within 24 h and within 48 h, respectively. Conclusions Appropriate release times were estimated and compared using different criteria. Most patients could have been released without isolation or within 24 h of radiation treatment.