Background Cognitive impairment (CI) is one of the most prevalent symptoms of multiple sclerosis (MS). However, it is difficult to include cognitive assessment as part of MS standard care since the comprehensive neuropsychological examinations are usually time-consuming and extensive. Objective To improve access to CI assessment, we evaluated the feasibility and potential assessment sensitivity of a tablet-based cognitive battery in patients with MS. Methods In total, 53 participants with MS (24 [45%] with CI and 29 [55%] without CI) and 24 non-MS participants were assessed with a tablet-based cognitive battery (Adaptive Cognitive Evaluation [ACE]) and standard cognitive measures, including the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). Associations between performance in ACE and the SDMT/PASAT were explored, with group comparisons to evaluate whether ACE modules can capture group-level differences. Results Correlations between performance in ACE and the SDMT (R=–0.57, P<.001), as well as PASAT (R=–0.39, P=.01), were observed. Compared to non-MS and non-CI MS groups, the CI MS group showed a slower reaction time (CI MS vs non-MS: P<.001; CI MS vs non-CI MS: P=.004) and a higher attention cost (CI MS vs non-MS: P=.02; CI MS vs non-CI MS: P<.001). Conclusions These results provide preliminary evidence that ACE, a tablet-based cognitive assessment battery, provides modules that could potentially serve as a digital cognitive assessment for people with MS. Trial Registration ClinicalTrials.gov NCT03569618; https://clinicaltrials.gov/ct2/show/NCT03569618