OBJECTIVES: DMTs constitute an important backbone of MS treatment. To investigate Health Related Quality of Life (HRQOL) and patient adherence rates to the approved DMTs for RRMS among geographically and  culturally diverse patient populations, a multinational study was to be implemented. Operational and scientific outcomes are presented. METHODS: The study was designed as an observational, multicenter, multinational post marketing study. Patients and physicians received paper questionnaires evaluating adherence to DMTs approved at the time of the study. HRQOL (MusiQol) and a Neuropsychological Questionnaire (MSNQ) also were applied. RESULTS: The study was implemented in 22 countries. Special challenges: cross-cultural CRF design, country-specific recruitment procedures for sites and patients, country/site specific contractual arrangements. Ethical approval was collected from 70 local and 15 central institutions. Patient recruitment was performed via 176 neurologists (hospital and office based). In total, 2.566 patients were enrolled within 6 months. Average treatment duration / observational period covered 31 months. The study findings revealed that 75% of the patients were adherent (i.e. not missing an injection or changing dose). 12.6% of all patients forgot to administer injections compared to 50% of non-adherent patients.  Compared to non-adherent patients, adherent patients showed shorter disease duration (adherent: median 6.0 yrs; non-adherent: Median 7.0 yrs.), significant shorter treatment time (30.0 months vs. 36.0 months; p<0,001) and a better MSNQ score (18.0 vs. 22.0; p<0,001). CONCLUSIONS: For implementing a global multicenter center important issues include: linguistic specifics for CRF development, availability of medical centers for site recruitment, country specific legal and ethical requirements, careful organization and sharing of responsibilities between the study coordination center and local affiliates.  Non-adherence to DMT in RRMS was demonstrated to be mainly caused by injection problems; adherent patients showed better clinical and HRQOL outcomes.