A rare case of pleural empyema caused by Leuconostoc spp. is reported. The patient was treated successfully with clindamycin. To our knowledge this is the first reported case of pleural empyema caused by Leuconostoc spp. in a patient with characteristic predisposing factors, such as a serious underlying disease, previous vancomycin therapy and thoracic access device. Our case illustrates that Leuconostoc spp. can cause pleural infection as further evidence of its human pathogenecity.