Background: Multiple sclerosis (MS) is a chronic progressive degenerative disease that affects the myelin sheath of the neurons in the central nervous system. Self-management is essential for people with MS because it helps them improve their prognosis by learning about the different elements of the condition and regularly monitoring their health with their caregivers. The study was aimed to evaluate the effect of educational guideline on self-management and clinical outcomes for patients with MS. Study design: A quasi-experimental design was utilized to conduct this study. Setting: This study was conducted at Multiple Sclerosis Outpatient Clinic affiliated to Ain Shams University Hospital, Egypt. Sample: A purposive sample of 80 adult patients were selected based on inclusion criteria. Tools of data collection: An interview questionnaire to assess patient's demographic characteristics and patient's clinical data. Patients' knowledge assessment. Multiple Sclerosis Self-Management Scale. Clinical Outcomes Assessment Questionnaire. Results: The mean age of the studied patients was 36.75 ± 5.63; females were more prevalent and constituted 68.8% of the studied patients. Also, 88.8% and 87.5% of them had satisfactory level of total knowledge and total self-management practices post implementation of educational guideline, respectively. Moreover, there was a significant reduction in impact of fatigue, pain, visual impairment and psychological distress among the studied patients post implementation of educational guideline. Furthermore, there was a significant improvement in patients' bladder, bowel control, sexual activity and satisfaction post implementation of educational guideline. Conclusion: The implementation of educational guideline has a statistically significant positive effect on self-management and clinical outcomes for patients with MS. Recommendations: Self-management guideline should be included in the routine nursing care and rehabilitation process for patients with MS and should be updated periodically in order to enhance their knowledge and self-management practices. Establishment of Web site under medical and nursing supervision to provide information about the disease.