Background and purpose: In relapsing‐remitting multiple sclerosis patients (RRMS) disability progressively accumulates over time. To compare the cumulative probability of 6‐month confirmed disability‐worsening events using a fixed baseline or a roving Expanded Disability Status Scale (EDSS) reference, in a real‐world setting. Methods: A cohort of 7964 RRMS patients followed for 2 or more years, with EDSS scores recorded every 6 months, was selected from the Italian Multiple Sclerosis Register. The overall probability of confirmed disability‐worsening events and of confirmed disability‐worsening events unrelated to relapse was evaluated using as reference a fixed baseline EDSS score or a roving EDSS score in which the increase had to be separated from the last EDSS assessment by at least 6 or 12 months. Results: Using a fixed baseline EDSS reference, the cumulative probability of 6‐year overall confirmed disability‐worsening events was 33.2%, and that of events unrelated to relapse was 10.9% (33% of overall confirmed disability‐worsening events). Using a roving EDSS, the proportions were respectively 35.2% and 21.3% (61% of overall confirmed disability‐worsening events). Conclusions: In a real‐world setting, roving EDSS reference scores appear to be more sensitive for detecting confirmed disability‐worsening events unrelated to relapse in RRMS patients. [ABSTRACT FROM AUTHOR]