ABSTRACT Although ample evidence exists that shift-work is dangerous for patients and nurses, very little is known about optimal shift scheduling. Experiments which quantify the fatigue-related risks associated with shiftwork are desperately needed to inform policy regulating shift scheduling. To meet this need, we propose a study to determine the impact of shift-accumulated fatigue on the spectrum of daily activities nurses engage in: from patient care to post-shift drive home. The proposed between-groups, repeated- measures quasi-experiment will be conducted in the Washington State University (WSU) College of Nursing and Sleep and Performance Research Center. Nurse participants (N=100) will report to WSU for testing on two separate occasions—once immediately following their 3rd consecutive 12-hour shift and once on their 3rd consecutive day (72 hours) off work. Conditions will be counterbalanced among participants to control for learning effects. Testing will include a 10-minute Psychomotor Vigilance Task (PVT) to objectively measure their fatigue, the Karolinska Sleepiness Scale (KSS) to measure subjective sleepiness, 90 minutes of critical skills in our nursing simulation lab (including IV insertion, medication calculation, and quality of patient care), and a 20-minute drive in one of our driving simulators (to simulate a “post-shift” drive home). During testing, participants will be fitted with functional near infrared (fNIR) optical brain imaging and mobile eye gaze tracking devices to assess the impact of fatigue on cognitive workload and visual processing respectively. Participants will be fitted with wrist actigraphs to objectively measure their sleep throughout the study. Using this innovative design, our specific aims are to: 1) measure the within-participant impact of shift- accumulated fatigue on nursing simulation critical skills; 2) measure the between-participant impact of day vs. night shifts on nursing simulation critical skills; and, 3) quantify the risk of collisions to nurses driving home post shift. The proposed research will provide objective evidence of the impact of shift work on nurses’ patient care-related critical skills and risk of collisions during their post-shift drive home. This will result in concrete recommendations regarding safe shift-scheduling for day and nightshift nurses. The information we generate may provide the push needed to set national work hour policies for nurses. Given that doctors have had regulations on work hours since 1987 it is unacceptable that nurses still do not have set policies protecting them against safety risks and protecting their patients against preventable medical errors. The proposed study could be an important, timely, and nationally relevant step towards addressing this critical gap in health care.