BACKGROUND: The aim of this study was to investigate the dynamics of annual whole brain volume loss (BVL/year) and annual thalamic volume loss (ThalaVL/year) in patients with relapsing-remitting multiple sclerosis (PwRRMS) during the course of the disease. METHODS: A longitudinal database of magnetic resonance imaging (MRI) scans of 195 healthy individuals (age range, 22.8-63.7 years) and longitudinal MRI data of 256 PwRRMS (age range, 20.1-60.8 years) were analyzed and compared. BVL/year and ThalaVL/year were computed for healthy individuals as well as for all patients with MS using a Jacobian integration approach. A linear regression was used to compute the relationship between age and BVL/year and ThalaVL/year for healthy individuals. The linear regression was then used to decompose the BVL/year and ThalaVL/year into a multiple sclerosis (MS)-related and an age-related component for each PwRRMS. PwRRMS were dichotomized into early-phase RRMS (disease duration ≤ 6 years) and later-phase RRMS (disease duration > 6 years), and a t-test was performed to test for differences between these groups. RESULTS: The 135 early-phase patients (disease duration, ≤ 6 years) had statistically significantly higher MS-related BVL/year than the later-phase patients (n = 121) (- 0.21% vs. - 0.06%, p = 0.007). For MS-related ThalaVL/year, the difference between the groups was even more pronounced (- 0.39% vs. - 0.00%, p < 0.0001). CONCLUSIONS: Our results indicate that in PwRRMS, the MS-related components of BVL/year and ThalaVL/year are accelerated in early phases and slowdown in later phases of the disease. This might explain why early intervention often leads to improved outcomes in patients with MS.