Study Objectives: There is a long-standing debate about the best way to characterize performance deficits on the psychomotor vigilance test (PVT), a widely used assay of cognitive impairment in human sleep deprivation studies. Here, we address this issue through the theoretical framework of the diffusion model and propose to express PVT performance in terms of signal-to-noise ratio (SNR). Methods: From the equations of the diffusion model for one-choice, reaction-time tasks, we derived an expression for a novel SNR metric for PVT performance. We also showed that LSNR-a commonly used log-transformation of SNR-can be reasonably well approximated by a linear function of the mean response speed, LSNR apx . We computed SNR, LSNR, LSNR apx , and number of lapses for 1284 PVT sessions collected from 99 healthy young adults who participated in laboratory studies with 38 hr of total sleep deprivation. Results: All four PVT metrics captured the effects of time awake and time of day on cognitive performance during sleep deprivation. The LSNR had the best psychometric properties, including high sensitivity, high stability, high degree of normality, absence of floor and ceiling effects, and no bias in the meaning of change scores related to absolute baseline performance. Conclusions: The theoretical motivation of SNR and LSNR permits quantitative interpretation of PVT performance as an assay of the fidelity of information processing in cognition. Furthermore, with a conceptual and statistical meaning grounded in information theory and generalizable across scientific fields, LSNR in particular is a useful tool for systems-integrated fatigue risk management.