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The authors performed a prospective safety and feasibility study in 100 consecutive patients undergoing glymphatic MR imaging from September 2015 to August 2018. Short- and long-term serious and nonserious adverse events were registered clinically and by interview after intrathecal administration of 0.5 mL of gadobutrol (1.0 mmol/mL) along with 3 mL of iodixanol (270 mg I/mL). One serious adverse event (anaphylaxis) occurred in a patient with known allergy to iodine-containing contrast agents (1%). The main nonserious adverse events during the first 1–3 days after contrast injection included severe headache (28%) and severe nausea (34%), though the frequency depended heavily on the diagnosis. They conclude that intrathecal administration of gadobutrol in conjunction with iodixanol for glymphatic MR imaging is safe and feasible.