The aim of this research was to assess the level of adaptation to multiple sclerosis (Sclerosis multiplex; MS) and health-related quality of life (HRQoL) of the study population as well as to determine the relationship between biomedical factors related to the course of multiple sclerosis, adaptation to the disease, and HRQoL. Analysis of medical records, clinical and psychological interviews, the Extended Disability Status Scale (EDSS), Guy’s Neurological Disability Scale (GNDS), the Acceptance of Illness Scale (AIS), and the Multiple Sclerosis Impact Scale 29 (MSIS-29) were collected from 137 patients with MS. It was found that there was a relation between motor impairment, neurological disability, adaptation to illness, and HRQoL; it was also found that there were negative correlations between adaptation to illness and the severity of lower-limb disability, fatigue, mood disorders, other problems related to MS, and upper-limb disability. Of all the symptoms, lower-limb disability, fatigue, and mood disorders had the strongest relation with adaptation. All of the analysed symptoms were found to correlate with HRQoL. Of all the symptoms, HRQoL was most affected by lower- and upper-limb disability, fatigue, other MS problems, and mood disorders.