Staphylococcus lugdunensis, a coagulase-negative Staphylococcus species, is an increasingly relevant pathogen in the clinical setting. The organism has been isolated as a source of multiple clinical manifestations, including endocarditis. Herein, the authors present 2 cases of Staphylococcus lugdunensis endocarditis. These cases demonstrate the enhanced virulence and wide range of disease severity this organism creates. This enhanced virulence, undoubtedly present in these cases, led to novel daptomycin antibiotic regimen. To the best of the authors knowledge, these are the first reported cases using daptomycin in the treatment of Staphylococcus lugdunensis endocarditis.