Purpose: Although, captopril scintigraphy is a well established method to detect renovascular hypertension, the optimal radiopharmaceutical for this test remains to be determined. Recently, Tc-99m ethylenedicysteine (Tc-99m EC) appeared as an alternative agent for captopril scintigraphy. The aim of this study was to compare the diagnostic accuracy of Tc-99m EC with Tc-99m DTPA, which is a well-established renal radiopharmaceutical for the captopril test. Methods: Nineteen hypertensive patients who had various degrees of renal artery stenosis on angiography were included in the study. All patients had baseline and captopril Tc-99m EC and Tc-99m DTPA scintigraphy within a 1- week period. The results were compared with angiography and in eight patients with changes in blood pressure after revascularization. The images were interpreted without knowledge of the angiography and revascularization data as low, intermediate, or high probability for hemodynamically significant renal artery stenosis, which was defined as an area of stenosis exceeding 50%. Results: Tc-99m EC and Tc-99m DTPA study results were in agreement in 16 of the 19 patients. In two patients with branch artery stenosis, Tc-99m EC was definitely superior to Tc-99m DTPA and correctly identified the probability of stenosis on scintigraphy. On kidney analysis, Tc-99m EC had a slightly greater diagnostic sensitivity compared with Tc-99m DTPA (79% vs. 68%; P > 0.05 by the chi-squared test) but equal specificity (93% for both agents). Both Tc-99m EC and Tc-99m DTPA showed the same accuracy in predicting the outcome after revascularization in all but one patient with branch artery stenosis, in whom Tc-99m EC accurately predicted a successful outcome of the intervention but Tc-99m DTPA did not. Tc-99m EC had better renal uptake in patients with decreased renal function and provided more dramatic evidence of renogram changes after captopril intervention, which resulted in more confident interpretation. Conclusions: There is no significant difference between Tc-99m EC and Tc-99m DTPA captopril scintigraphy for detecting renal artery stenosis. However, because of the better imaging characteristics and more confident interpretation provided by the dramatic changes in the degree of renogram abnormality after captopril intervention, Tc-99m EC captopril scintigraphy should be used, particularly in patients with decreased renal function or branch artery stenosis.