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• Sexual dysfunction prevalence varies according to the instrument and cut-off applied. • Severe involvement of one sexual domain is associated with motor and cognitive function. • Involvement of many sexual domains is associated with age, anxiety and cognitive function. • Cognitive preservation and rehabilitation could aid in presence of sexual dysfunction. Although multiple sclerosis (MS) Intimacy and Sexuality Questionnaire-19 (MSISQ-19) is a widely applied tool, no unique definition of sexual dysfunction (SD) based on its score exists. To explore the impact of different MSISQ-19 cut-offs on SD prevalence and associated risk factors, providing relevant information for its application in research and clinical settings. After defining SD according to two different MSISQ-19 cut-offs in 1155 people with MS (pwMS), we evaluated SD prevalence and association with sociodemographic and clinical features, mood status and disability via logistic regression. Depending on the chosen cut-off, 45% to 54% of pwMS reported SD. SD defined as MSISQ-19 score >30 was predicted by age (OR=1.01, p=0.047), cognition (OR=0.96, p=0.004) and anxiety (OR=1.03, p=0.019). SD defined as a score >3 on any MSISQ-19 item was predicted by motor disability (OR=1.12, p=0.003) and cognition (OR= 0.96, p=0.002). Applying different MSISQ-19 cut-offs influences both the estimated prevalence and the identification of risk factors for SD, a finding that should be considered during study planning and data interpretation. Preserved cognition exerts a protective effect towards SD regardless from the specific study setting, representing a key point for the implementation of preventive and therapeutic strategies. [ABSTRACT FROM AUTHOR]