BackgroundMuscle weakness is common and significantly affects persons with multiple sclerosis (PwMS), with dysfunction in upper limb (UL) muscle groups occurring in approximately 60% of PwMS.ObjectiveTo develop gender‐specific regression‐based prediction equations, with 95% confidence intervals for maximal bilateral UL isometric strength (shoulder abduction and adduction, wrist flexion and extension) and hand grip strength in PwMS.DesignCross‐sectional study.SettingComprehensive MS center.Participants256 PwMS.InterventionsNot Applicable.Main Outcome MeasuresShoulder abduction and adduction and wrist flexion and extension isometric strength (Biodex System 4 Pro Dynamometer) and hand grip strength (Jamar handheld dynamometer) were measured. Disease characteristics (disability and disease duration) and demographics (age, height, and weight) were collected. Regression‐based predictive equations were generated for the UL muscle groups for each gender and limb, using age, height, weight, disability, and disease duration as covariates. Variables were compared between genders using the Mann–Whitney U test. Maximal voluntary contraction (MVC) reference values (mean ± SD) were reported based on age (<30, 30–39, 40–49, 50–59, 60–69 years) and disability (mild, moderate, severe ambulant, and severe nonambulant) for each gender and limb.ResultsRegression‐based equations were developed for both genders' strongest and weakest limb, accounting for age, height, weight, disability, and disease duration. MVC was higher in men than women (p < .001) in all muscle groups. Overall, MVC was significantly related to age in 14, height in 5, weight in 6, disability in 14, and disease duration in none of the 20 models.ConclusionThis is the first study to provide regression‐based prediction equations for strongest and weakest MVC of UL muscle groups and demonstrated an inverse relationship between MVC with disability and age. Regression‐based reference strength values can help clinicians understand muscular strength along a spectrum of PwMS and can aid in goal setting and education for realistic outcomes.