Background and Objectives: Neurofilament light chain (NfL) is a sensitive biomarker of neuroaxonal damage. This study aimed to assess the relationship between the annual change in plasma NfL (pNfL) and disease activity in the past year, as defined by the concept no evidence of disease activity (NEDA) in a cohort of multiple sclerosis (MS) patients.Materials and Methods:Levels of pNfL (SIMOA) were examined in 141 MS patients and analyzed in relationship to the NEDA-3 status (absence of relapse, disability worsening, and MRI activity) and NEDA-4 (NEDA-3 extended by brain volume loss ≤ 0.4%) during the last 12 months. Patients were divided into two groups: annual pNfL change with an increase of less than 10% (group 1), and pNfL increases of more than 10% (group 2).Results:The mean age of the study participants (n= 141, 61% females) was 42.33 years (SD, 10.17), and the median disability score was 4.0 (3.5–5.0). The ROC analysis showed that a pNfL annual change ≥ 10% correlates with the absence of the NEDA-3 status (p< 0.001; AUC: 0.92), and the absence of the NEDA-4 status (p< 0.001; AUC: 0.839).Conclusions:Annual plasma NfL increases of more than 10% appear to be a useful tool for assessing disease activity in treated MS patients.