Background: To examine the effect of optic disc area on peripapillary RNFLT (retinal nerve fiber layer thickness) measurement at circle diameter of 3.4 mm around optic nerve head using spectral OCT/SLO (Optical coherence tomography/scanning laser ophthalmoscope). Materials and Methods: In this prospective, cross sectional study, one hundred and two eyes of 102 normal subjects underwent RNFLT and disc area measurement using spectral OCT/SLO. Based on disc area, subjects were divided into three groups i.e., <3 mm(2) (32 eyes), 3-4 mm(2) (36 eyes) and >4 mm(2) (34 eyes). The effect of disc area on RNFLT parameters was analyzed using linear regression analysis. Results: The mean and quadrant RNFLT did not show significant correlation with disc area in subjects with disc area of <4 mm(2), however in eyes with disc area >4 mm(2), average RNFLT, superior and temporal quadrant RNFLT showed negative correlation with disc area, which was statistically significant (P = 0.004, P = 0.005 and P = 0.002, respectively) Conclusion: In healthy eyes of disc area <4 mm(2), disc size does not appear to affect peripapillary RNFLT measurement by spectral OCT/SLO. Average, superior and temporal quadrant RNFLT measurements were inversely proportional to disc area in eyes with disc area >4 mm(2). Hence, RNFLT measurement by OCT in eyes with optic disc area of >4 mm(2) should be interpreted carefully.