To assess the efficacy of an early thallium-201 reinjection protocol for reducing the need for late redistribution imaging, the frequency of thallium-201 late reversibility was prospectively assessed in 62 patients who had stress-redistribution thallium-201 studies by single-photon emission computerized tomography (SPECT), and who received 1 mCl of thallium-201 reinjection immediately following stress tomographic acquisition. These patients also demonstrated ≥2 segments with nonreversible defects at 4-hour imaging and underwent late (18-to 72-hour) redistribution imaging. When the criterion of late reversibility was defined as ≥1 segment with a 4-hour nonreversible defect demonstrating late reversibility, late reversibility was present in 36 (58%) of the 62 patients and in 88 (24%) of 368 SPECT segments. When the criterion of ≥2 segments was used, late reversibility was found in 21 (34%) of the 62 patients and in 73 (20%) of the 368 segments. Of the 21 patients who had ≥2 late reversible segments, 12 (57%) exhibited late reversibility in ≥3 segments. The frequency of detected reversible defects increased from 32% by 4-hour imaging to 48% by combined 4-hour and late imaging (p < 0.0001). The patients who demonstrated late reversibility could not be distinguished from those who had only late nonreversible defects by analysis of the clinical, exercise, and electrocardiographic (ECG) variables. The frequency of patients and myocardial segments demonstrating late reversibility following early thallium-201 reinjection was shown to be similar to that previously observed in thallium-201 SPECT studies without reinjection. In conclusion, thallium-201 reinjection immediately following poststress imaging did not reduce the frequency of late reversibility. The comparative results of the present and other studies suggest that thallium-201 reinjection just prior to 4-hour redistribution imaging may be more effective in reducing the incidence of late reversibility.