Patients with multiple sclerosis (MS) experience various physical symptoms and psychosocial problems that disrupt their normal life, and adapting to these conditions is vital for them. Many factors that serve as facilitators of and barriers to achieving adjustment should be identified to be able to help the patients. This study was conducted to explain the experiences of patients with MS regarding the facilitators of and barriers to adjustment using conventional content analysis. The participants consisted of 18 patients, one nurse, one physician, and one patient companion, who were selected from the Multiple Sclerosis Clinic of BouAli, northern Iran, through purposive sampling. Data were collected through individual, in-depth, and semi-structured interviews and analyzed using the method recommended by Elo and Kyngäs (2008). The data analysis generated five subcategories as facilitators and five subcategories as barriers. The subcategories of facilitators included family’s appropriate behavior with the patient, occupation, studying and information gathering, religious beliefs, and turning attitude into disease simplification and optimism. The subcategories of barriers were concerns about the uncertain future of the disease, physicians’ poor communication and behavior, society’s poor attitude, economic problems, and unsatisfactory support by the government and insurance companies. The results showed that a set of individual, environmental, and social factors serves as facilitators of or barriers to the process of adjustment to MS in patients. Gaining knowledge about these factors in congruence with the sociocultural context of the society, as derived from people’s real experiences, can help healthcare staff and the family of these patients provide more efficient assistance to the patients for achieving adjustment earlier.