Purpose To compare measurements of the full-field photopic negative response (PhNR), as well as intra-subject variation in the PhNR, using time and time-frequency domain analyses. Methods Full-field ERGs were recorded from 20 normally-sighted subjects (ages 24 to 65 years) elicited by a long-wavelength pulse (3 cd s m−2) presented against a short wavelength adapting field (12.5 cd m−2). Three to 10 waveforms were obtained from each subject and each waveform was analyzed using standard time domain analyses of the PhNR, as well as a discrete wavelet transform (DWT) to extract time-frequency components that correspond to the PhNR. Three different measures of the PhNR were derived and compared: 1) amplitude at the PhNR trough; 2) amplitude at 72 ms following stimulus onset; 3) energy in the 11 Hz, 60 to 120 ms DWT frequency bin that corresponds to the PhNR. In addition, the effect of normalizing the PhNR by the b-wave was evaluated for each of the measures. Coefficients of variation (CVs) were computed for each definition to evaluate intra-subject variation. Results PhNR amplitudes measured at the trough and at 72 ms were significantly correlated (r = 0.88, p < 0.001). Additionally, PhNR energy derived by DWT was significantly correlated with the amplitude measured at the trough (r = 0.64, p = 0.002) and at 72 ms (r = 0.60, p = 0.005). Mean (± SD) intra-subject CVs were 26% (15%), 49% (26%), and 30% (15%), for measures at the trough, 72 ms, and DWT, respectively. Normalization by the b-wave amplitude (i.e. PhNR/b) had minimal effect on the intra-subject CVs, whereas normalization by the sum of the b-wave and PhNR amplitudes (i.e. PhNR/[b+PhNR]) substantially reduced the CVs for all three measures (mean CVs were less than 17% for all conditions). Conclusions Although each PhNR definition has advantages and disadvantages, all three metrics provide similar estimates of the PhNR. Intra-subject CVs, however, were relatively high for measurements made at 72 ms, indicating that definitions based on a fixed time-point may introduce variability. The substantial decrease in intra-subject variation after normalization by the sum of the PhNR and b-wave amplitudes may be advantageous under some conditions.