Background: Nursing is an occupation with high risk of musculoskeletal injury. Nurses' perceptions of the risk of injury have a role in preventing such injury. Uses of proper body mechanics reduce risk of injury to the musculoskeletal system. Aim of the study was to evaluate the effect of educational program on nurses' performance regarding body mechanics. Subject and Methods: Research design: A quasi experimental research design was used. Setting: The study was conducted in the Intensive Care Units, Dialysis Units, Orthopedic Units and Surgical Units at Zagazig University Hospital. Subjects: composed of 76 nurses who performing actual patient care. Tools of data collection: Four tools were used to collect data included nurses interviewing assessment questionnaire, body mechanics observational checklist, nurses' pain assessment questionnaire and Oswestry low back pain disability questionnaire. Results: revealed that, the majority of studied nurses had back pain and all studied nurses had no training course of body mechanics. There was highly statistically significant difference between pre/post and pre/follow up program phase as regarding to nurses' knowledge, practice, pain intensity and disability but some decline occurred in the follow up program phase compared with post phase. Conclusion: The effect of health educational program had improved nurses' knowledge, practice regarding body mechanics, pain intensity and disability. Recommendations: Educational programs should be held periodically for nurses on proper body mechanics and correct lifting techniques should be introduced in the workplace to reduce the burden of musculoskeletal pain among the nurses working in different setting.