Background: Early detection and monitoring of cognitive dysfunction in multiple sclerosis (MS) may be enabled with smartphone-adapted tests that allow frequent measurements in the everyday environment. Objectives: The aim of this study was to determine the reliability, construct and concurrent validity of a smartphone-adapted Symbol Digit Modalities Test (sSDMT). Methods: During a 28-day follow-up, 102 patients with MS and 24 healthy controls (HC) used the MS sherpa ® app to perform the sSDMT every 3 days on their own smartphone. Patients performed the Brief International Cognitive Assessment for MS at baseline. Test–retest reliability (intraclass correlation coefficients, ICC), construct validity (group analyses between cognitively impaired (CI), cognitively preserved (CP) and HC for differences) and concurrent validity (correlation coefficients) were assessed. Results: Patients with MS and HC completed an average of 23.2 (SD = 10.0) and 18.3 (SD = 10.2) sSDMT, respectively. sSDMT demonstrated high test–retest reliability (ICCs > 0.8) with a smallest detectable change of 7 points. sSDMT scores were different between CI patients, CP patients and HC (all ps < 0.05). sSDMT correlated modestly with the clinical SDMT (highest r = 0.690), verbal (highest r = 0.516) and visuospatial memory (highest r = 0.599). Conclusion: Self-administered smartphone-adapted SDMT scores were reliable and different between patients who were CI, CP and HC and demonstrated concurrent validity in assessing information processing speed.