Automation technique has been widely used in manufacturing industry, but there are still manual handling operations required in assembly and maintenance work in industry. Inappropriate posture and physical fatigue might result in musculoskeletal disorders (MSDs) in such physical jobs. In ergonomics and occupational biomechanics, virtual human modelling techniques have been employed to design and optimize the manual operations in design stage so as to avoid or decrease potential MSD risks. In these methods, physical fatigue is only considered as minimizing the muscle or joint stress, and the fatigue effect along time for the posture is not considered enough. In this study, based on the existing methods and multiple objective optimisation method (MOO), a new posture prediction and analysis method is proposed for predicting the optimal posture and evaluating the physical fatigue in the manual handling operation. The posture prediction and analysis problem is mathematically described and a special application case is demonstrated for analyzing a drilling assembly operation in European Aeronautic Defence & Space Company (EADS) in this paper.