AIM: To systematically evaluate the effect of work schedule characteristics on fatigue among shift nurses in hospital settings. BACKGROUND: The complexity and multidimensional nature of nursing work may lead to fatigue. This review mainly focused on work schedule characteristics that may mitigate the fatigue in nurses. EVALUATION: Six databases were searched and 8 relevant research articles published between 2000 and 2018 were identified. KEY ISSUES: The reviewed articles provided some evidence supporting the association of work schedule characteristics such as total working hours, overtime, shift length, and number of monthly night and evening shifts with fatigue. In addition, studies provided evidence for the positive association between insufficient rest period between shifts and fatigue among shift nurses in hospital settings. CONCLUSION: The reviewed studies provided mixed results regarding the associations between work schedule characteristics and nurse fatigue. However, quick returns and days called to work on days off were consistent factors contributing to nurse fatigue. More evidence is needed to arrive at a definitive conclusion about such relationships. IMPLICATION FOR NURSING MANAGEMENT: Nursing managers and administrators need to carefully review current rotating shift system and examine its impact on nurse fatigue as well as ensure enough resting time when developing nurse schedules. This article is protected by copyright. All rights reserved.