Purpose: To evaluate the measurements of the peripapillary retinal neurofiber layers (RNFL) and the ganglion cells complex (GCC) obtained by Optical Coherence Tomography (OCT) in eyes with preperimetric open-angle glaucoma. Methods: One hundred and forty eyes of 75 patients (21 male and 54 female), 80 eyes with preperimetric glaucoma (PPG) (45 patients) and 60 normal eyes (30 subjects) were included in this study. Automated visual field examination was done to all participants using Humphrey field analyzer, program 30-2. The GCC thickness and peripapillary RNFL thickness were measured using RTVue-100 (Optivue, Inc., Fremont, CA). The areas under ROC (receiver operating characteristic)—curves (AUCs) were defined for all examined GCC and RNFL parameters. Results: GCC of the eyes with PPG was significantly thinner than GCC of the normal eyes: (89.58 vs 97.82 microns, P < 0.001). There was no significant difference between upper and lower GCC halves in both study groups. We found a reduction of RNFL thickness in glaucomatous eyes (P < 0.001) compared with normals. AUCs for GCC parameters in eyes with PPG were larger than AUCs for RNFL parameters. Conclusion: Our study showed that the peripapillary RNFL and GCC thickness are lower in preperimetric glaucoma than in normal eyes. Despite the fact that GCC measurements (especially GLV) show better AUC than peripapillary measurements, we suggest that two scans (GCC and ONH) put together are superior in detecting early structural glaucomatous damage. Several diagnostic parameters should be considered in the clinical diagnosis of preperimetric glaucoma.