Repositioning patients in bed is the most common patient handling activity and is associated with musculoskeletal disorders in caregivers. Hospital bed features may mitigate the risk of injury. The current study investigated the effect of bed features on the physical stress on caregivers. Ten nurses were recruited to perform three repositioning activities. Hand forces were recorded, and spine loading was estimated using a dynamic biomechanical model. Results demonstrated that except for the peak L5/S1 compressive load in the turning task, the use of assistive features significantly reduced the physical stresses for all repositioning activities. However, recommended thresholds for injury were still exceeded in many conditions. Compared with spinal load, hand force was much higher relative to the injury thresholds, suggesting a greater risk of shoulder and upper extremity injuries than low back injury. Mechanical lift equipment remains the safest and most robust way to reposition a patient.