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The best strategy to perform follow-up of patients with multiple cerebral cavernous malformations (mCCM) is unclear due to the unpredictable clinical course. Still, serial radiological follow-up is often performed. The objective of this work was to critically question whether active follow-up by serial imaging is justified and has an impact on clinical decision making. We included all consecutive patients with mCCM treated and followed at our Department between 2006 and 2016. Patient data were collected and analyzed retrospectively. From a total number of 406 patients with CCM, = 73 [18.0%; mean age at first diagnosis 45.2 years (±2.4 SE); = 42 male (57.5 %)] were found to harbor multiple lesions (≤5 CCM in 58.9%; 6-25 in 21.9%; ≥ 25 in 19.2%). All of them were followed for a mean of 6.8 years (±0.85 SE). Conservative treatment was suggested in 43 patients over the complete follow-up period. Thirty patients underwent surgical extirpation of at least one CCM lesion. Forty-three surgical procedures were performed in total. During 500.5 follow-up years in total, routinely performed follow-up MRI in asymptomatic patients lead to an indication for surgery in only two occasions and even those two were questionable surgical indications. Routinely performed follow-up MRI in asymptomatic patients with mCCM is highly questionable as there is no evidence for therapeutic relevance.