Objective The aim of the study was to estimate the risk of injury when repositioning patients of different weight with commonly used repositioning aids. Background Repositioning dependent patients in bed is the most common type of patient handling activity and is associated with high rates of musculoskeletal disorders in healthcare workers. Several studies have evaluated repositioning aids, but typically for a single patient weight and often without estimating risk of injury based on biomechanical analysis. Method Ten nurses performed four repositioning activities on three participants (50, 77, 141 kg) using three repositioning aids (pair of friction-reducing sheets [FRS], turn and position glide sheet, air-assisted transfer device) and a draw sheet. Motion capture, hand forces, and ground reaction forces were recorded. Spine loading was estimated using a dynamic biomechanical model. Results Hand forces and spine compression exceeded recommended limits for most patient weights and repositioning tasks with the draw sheet. FRS and glide sheet reduced these loads but still exceeded recommended limits for all but the 50-kg patient. Only the air-assisted transfer device reduced forces to accepted levels for all patient weights. Physical stresses were relatively low when turning patients. Conclusion Most repositioning aids are insufficient to properly mitigate risk of musculoskeletal injury in healthcare workers. Only the air-assisted transfer device was sufficient to adequately mitigate the risk of injury when moving patients of average or above-average weight. Application To safely move dependent patients, a robust solution requires mechanical lifts and may utilize air-assisted transfer devices for patient transfers.