To evaluate and compare the diagnostic abilities of the speckle noise-reduced spectral-domain optical coherence tomography (SD-OCT; Spectralis OCT) and time-domain optical coherence tomography (TD-OCT; Stratus OCT) to detect localized retinal nerve fiber layer (RNFL) defects in patients with preperimetric open-angle glaucoma. Thirty-five eyes of 35 preperimetric glaucoma patients with localized RNFL defects and 72 normal control eyes were scanned using SD-OCT and TD-OCT. Areas under the receiver-operating characteristic curves (AUROCs), and the sensitivity and specificity for detecting localized RNFL defects based on the internal normative database of each device were calculated and compared. The AUROC for the best parameter from SD-OCT (inferotemporal sector, AUROC=0.940) was significantly higher than that of TD-OCT (7 o'clock sector, AUROC=0.881; P=0.009). The sensitivity of the SD-OCT parameters ranged from 18.9% to 83.8% and that of the TD-OCT parameters ranged from 5.4% to 54.1%, with the criterion of abnormal at the 5% level. The highest sensitivity of the SD-OCT was found with the temporal-superior-nasal-inferior-temporal thickness graph abnormal at the 5% level, which had a specificity of 90.3%. On the basis of temporal-superior-nasal-inferior-temporal thickness graphs, SD-OCT was more sensitive (P=0.001) for detection of preperimetric RNFL defects than TD-OCT at a comparable specificity (P=0.227). Speckle noise-reduced SD-OCT is better able to detect preperimetric localized RNFL defect(s) than TD-OCT.