Randomized clinical trials (RCT) in multiple sclerosis (MS) have a recent tradition, but their number has been exponentially increasing since the first study detecting the efficacy of a disease modifying drug in MS. To examine the methodological details of reports of RCT in MS, we extracted from five leading journals all the reports of RCT published between 1993 and 2010. Trial reports were compared for different periods (1993–2001, 2002–2006, 2007–2010) for a set of indicator variables reflecting methodological quality (including details about randomization and blinding, statistical methods, results reporting, subgroup analyses). Fifty-three reports were included in the analysis. All of the methodological items indicated an improvement over time in the quality of reporting, the main weaknesses being frequent and inappropriate use of significance testing for assessing baseline imbalances and the statistical approach to subgroup analysis. A complete and transparent reporting of trial methodology is becoming even more important in an era when new design strategies are required for the feasibility of future trials in MS.