Different angiographic patterns and restenosis rate may affect diagnostic value of single-photon emission computed tomography (SPECT) in the era of drug-eluting stents (DES). We aimed to determine the ability of myocardial SPECT to detect in-stent restenosis (ISR) in patients treated with DES compared to that of patients treated with bare metal stent (BMS). We evaluated 228 consecutive patients who underwent 6 months follow-up SPECT and coronary angiography (CAG) after stent implantation. In 228 patients, 354 vessels were treated with stent implantation (BMS, n = 105; DES, n = 249) and 65 (18.4%) vessels showed ISR (angiographic % diameter stenosis ≥ 50%) at the 6-month follow-up CAG. In patients with BMS-ISR (n = 37), restenosis was primarily diffuse (70.3%), whereas patients with DES-ISR (n = 28) exhibited more focal restenosis (53.6%, p = 0.028). The sensitivity and specificity of myocardial SPECT did not differ significantly between patients with BMS and those with DES (BMS vs. DES: sensitivity 56.8 vs. 39.3%, p = 0.163; specificity 72.1 vs. 76.5%, p = 0.460). Evaluation of 71 false positive and 33 false negative lesions showed that the most common cause of false-positive results in SPECT was the perfusion decrease which improved but not disappeared compared with the baseline (46 among 71 vascular territories). Despite different patterns of restenosis and ISR rates, the diagnostic value of SPECT did not differ between BMS and DES. Further study looking at ISR in larger number of patients and using other protocol such as Fleming-Harrington Redistribution Wash-in Washout may give additional information.