Late Onset Myoclonic Epilepsy in Down Syndrome (LOMEDS) is a recognized entity usually preceded by cognitive deterioration. We report two patients with LOMEDS and cognitive decline, aged 52 and 44 years. Continuous video-EEG recording showed generalised spike and slow wave complexes as an ictal correlate of the myoclonic jerks in both patients. Low dose levetiracetam resulted in rapid, sustained seizure freedom in both patients with no reported adverse events. As for other myoclonic epilepsies, levetiracetam appears to be effective for the treatment of LOMEDS, and may be considered as a first line agent for this disorder.