OBJECTIVES: To evaluate changes in patient reported fatigue and cognitive function after one year of natalizumab treatment in multiple sclerosis (MS) patients.  METHODS: The study population consists of MS patients initiating natalizumab treatment who agreed to participate in a 12 month longitudinal study.  Patients reported experiences with natalizumab using validated patient-reported outcome (PRO) measures prior to natalizumab treatment initiation (BL) and after 3rd, 6th and 12th infusion. The current analysis reports change in fatigue and cognition from baseline through the 12th natalizumab infusion. Fatigue was measured by the 5-question Modified Fatigue Impact Scale-5 (MFIS-5, score range 0-20) with lower scores indicating lower impact of fatigue on physical, cognitive, and psychosocial functioning; cognitive function was measured by the 6-question Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog Scale, score range 6-36) with higher scores indicating better reasoning skills, memory, concentration, ability to start several actions at one time and ability to react to what is said or done. Regression analysis was used to control for BL covariates such as age, years since MS diagnosis, number of natalizumab infusions received, disability and functional status, number of MS drugs used prior to natalizumab and comorbidity burden.  RESULTS: Data for 324 patients who completed the BL through 12th infusion assessments are reported. The mean age was 46.5 (SD=10.4) and the majority of patients were female (77.8%). The mean number of years since MS diagnosis was 10.16 (SD=8.23). On average, MFIS scores decreased significantly (BL 12.36+2.18; 12th infusion score 11.16+2.18, p<0.001) and MOS-Cog scores increased significantly over time (BL 25.12+1.51; 12th infusion score 26.19+1.97, p<0.001) after controlling for covariates.  CONCLUSIONS: MS patients reported improvements in fatigue and overall cognitive function after one year of natalizumab treatment.