Background <p>Positron emission tomography (PET) imaging of the 18&#xa0;kDa translocator protein (TSPO) is a method to quantify central inflammation and particularly microglial activation, which is increased in progressive multiple sclerosis (MS) among other neurodegenerative diseases. We evaluated the test-retest reproducibility of TSPO-PET imaging using Biograph Vision Quadra and [¹¹C]PK11195 radioligand. Three healthy volunteers and three people with progressive MS underwent two [¹¹C]PK11195-PET scans with a 1–3 day interval. TSPO binding was quantified as distribution volume ratios (DVR) using the supervised clustering algorithm. To evaluate the reproducibility of repeated [¹¹C]PK11195-PET scans, repeatability coefficients (RC) and intraclass correlation coefficients (ICC) were calculated.</p> Results <p>The ICCs indicated excellent test-retest reproducibility in distinct cortical regions (0.933–0.985) and white matter (0.980), and good to excellent test-retest reproducibility in deep grey matter structures (0.867–0.988). Additionally, the reproducibility was evaluated lesion-wise in the ≥50mm³ MS lesions (n=59). The test-retest reproducibility was good both at the lesion core (ICC 0.869) and rim (ICC 0.846). Conclusion: The test-retest reproducibility of [¹¹C]PK11195-PET using Biograph Vision Quadra is good to excellent among people with MS. This supports the usability of the ligand in longitudinal studies, including treatment trials.</p>