To determine whether an "optimal" distortion product otoacoustic emission (DPOAE) protocol that (1) used optimal stimulus levels and primary-frequency ratios for each f2, (2) simultaneously measured 2f2 - f1 and 2f1 - f2 distortion products, (3) controlled source contribution, (4) implemented improved calibration techniques, (5) accounted for the influence of middle ear reflectance, and (6) applied multivariate analyses to DPOAE data results in improved accuracy in differentiating between normal-hearing and hearing-impaired ears, compared with a standard clinical protocol. Data were collected for f2 frequencies ranging from 0.75 to 8 kHz in 28 normal-hearing and 78 hearing-impaired subjects. The protocol included a control condition incorporating standard stimulus levels and primary-frequency ratios calibrated with a standard SPL method and three experimental conditions using optimized stimuli calibrated with an alternative forward pressure level method. The experimental conditions differed with respect to the level of the reflection-source suppressor tone and included conditions referred to as the null suppressor (i.e., no suppressor tone presented), low-level suppressor (i.e., suppressor tone presented at 58 dB SPL), and high-level suppressor (i.e., suppressor tone presented at 68 dB SPL) conditions. The area under receiver operating characteristic (A(ROC)) curves and sensitivities for fixed specificities (and vice versa) were estimated to evaluate test performance in each condition. A(ROC) analyses indicated (1) improved test performance in all conditions using multivariate analyses, (2) improved performance in the null suppressor and low suppressor experimental conditions compared with the control condition, and (3) poorer performance below 4 kHz with the high-level suppressor. As expected from A(ROC), sensitivities for fixed specificities and specificities for fixed sensitivities were highest for the null suppressor and low suppressor conditions and lowest for standard clinical procedures. The influence of 2f2 - f1 and reflectance on test performance were negligible. Predictions of auditory status based on DPOAE measurements in clinical protocols may be improved by the inclusion of (1) optimized stimuli, (2) alternative calibration techniques, (3) low-level suppressors, and (4) multivariate analyses.