Objective: The objective of this study was to investigate whether the three-shift fast rotation, two-shift fast rotation and night-shift slow rotation led to any differences in fatigue and sleep quality. Method: The study was conducted as a beforeafter study and 17 nurses participated in the study. Nurses on three-shift fast rotation were allocated to the pre-group, and two-shift fast rotation and night-shift slow rotation were allocated to the post-group. In the study period, all of the subjects experienced the three patterns of rotation. Occupational Fatigue Exhaustion/Recovery Scale (OFER15) and Athens Insomnia Scale were used to measure the participants' work-related fatigue and sleep quality three times. Results: Athens Insomnia Scale scores showed significant differences between the three types of shift rotation; two-shift fast rotation was 3.88±2.35, three-shift fast rotation was 8.63 ± 3.50, and night-shift slow rotation was 13.75 ± 4.23 (P < 0.05). Therefore, the nurses' sleep quality through working on the two-shift rotation was better than the other two types of rotation. However, there were no significant differences in chronic fatigue, acute fatigue, and inter-shift [recovery] between the three types of rotations. Conclusion: Nurses who worked on the two-shift fast rotation had a better sleep quality than those who worked on the three-shift fast rotation and night-shift rotations. As sleep quality relates to the performance and alertness of nurses, greater attention should be paid to the use of different shift combinations to increase sleep quality and alertness. Considering sleep quality, a three-shift system arranged by two-shift fast rotation and combined with night-shift slow rotation is superior to the three-shift fast rotation.