Background: A spinal cord injury is a type of lesion to the spinal cord that can result in changes to its function, either permanently or temporarily. There are two categories of spinal cord injury aetiologies: traumatic and non-traumatic. This devastating illness can result in severe neurological damage and a lower standard of living. Aim of the study: To determine the effect of instructional guidelines on patients' knowledge, activities of daily living practices, and pain intensity following spinal cord injury. Research Design: A quasi-experimental design was used to fulfill the aim of the current study. Study Settings: The study was conducted in the neurological intensive care unit and neurology unit and neurology Outpatient Clinic at Sohag University Hospital. Subject: A convenient sample of (100) patients was selected from the previously selected settings.  Four tools for data collection: (1) Patient demographic data, (2) Patients' knowledge regarding spinal cord injury, (3) Patients' Activities of Daily Living practices regarding spinal cord injury, and (4) Numerical Pain Rating Scale. Result: The current study revealed that there was a highly statistically significant difference in patients' knowledge and practice, and reductions in pain mean scores among the studied patients post-instructional guidelines implementation compared to pre-instructional guidelines implementation with (P= <0.05). Also, the study demonstrated that there was a highly statistically significant correlation between patients' knowledge and practice, and pain intensity with (P= <0.001). Conclusion: The study concluded that instructional guidelines implementation for patients had a positive effect on improving patients' knowledge and activities of daily living practice and pain intensity following spinal cord injury with significant differences between pre and instructional guidelines implementation. Recommendation: Develop a simplified illustrated and comprehensive Arabic booklet to be available for all patients early when diagnosed including the latest information about spinal cord injury, its therapeutic regimen, and how the patients can manage their symptoms to improve their knowledge and Activities of Daily Living practices, and pain intensity.