Introduction: Work-related musculoskeletal disorders (WMSDs) include all injuries involving the locomotor system that occur at the job site, affecting soft tissue structures. Nursing is ranked as the top occupation among all the professions that have the potential to develop WMSDs and the prevalence among them ranges from 30% to 88%, depending on which body area is being considered. Aim of Work: To describe the pattern of WMSDs, to determine its prevalence among nurses at Main Assiut University Hospital, and to study the association between sociodemographic, work-related ergonomic risk factors, and the occurrence of WMSDs. Materials and Methods: A cross-sectional study was conducted among nurses at Main Assiut University Hospital during the period from January to July 2021. Data was collected using a questionnaire that included personal and detailed occupational history. The prevalence of musculoskeletal problems among the participants was determined using the Nordic Musculoskeletal Questionnaire (NMQ). The Dutch Musculoskeletal Questionnaire (DMQ) investigated the associated ergonomic risk factors. Results: Nearly 88% of the studied nurses were complaining of WMSDs throughout the previous 12 months of nursing practice. WMSDs affect mainly the low back (68.5%), and the elbow was the least affected site (22%). Emergency room nurses were the most affected group (96.7%), while ward nurses were the least ones (80.7%). Conclusion: There was a high prevalence of WMSDs symptoms among studied nurses at Main Assiut University Hospital (88%). The body region most frequently affected was the lower back, followedby the neck and knee while the elbow was the least frequently affected area