Objective. To estimate sensitivity and specificity of several optical coherence tomography (OCT) measurements for detecting retinal thickness changes in patients with relapsing-remitting multiple sclerosis (RRMS), such as macular ganglion cell-inner plexiform layer (GCIPL) thickness measured with Cirrus (OCT) and peripapillary retinal nerve fiber layer (pRNFL) thickness measured with Cirrus and Spectralis OCT. Methods. Seventy patients (140 eyes) with RRMS and seventy matched healthy subjects underwent pRNFL and GCIPL thickness analysis using Cirrus OCT and pRNFL using Spectralis OCT. A prospective, cross-sectional evaluation of sensitivities and specificities was performed using latent class analysis due to the absence of a gold standard. Results. GCIPL measures had higher sensitivity and specificity than temporal pRNFL measures obtained with both OCT devices. Average GCIPL thickness was significantly more sensitive than temporal pRNFL by Cirrus (96.34% versus 58.41%) and minimum GCIPL thickness was significantly more sensitive than temporal pRNFL by Spectralis (96.41% versus 69.69%). Generalised estimating equation analysis revealed that age ( P = 0.030 ), optic neuritis antecedent ( P = 0.001 ), and disease duration ( P = 0.002 ) were significantly associated with abnormal results in average GCIPL thickness. Conclusion. Average and minimum GCIPL measurements had significantly better sensitivity to detect retinal thickness changes in RRMS than temporal pRNFL thickness measured by Cirrus and Spectralis OCT, respectively.