high morbidity and mortality. The published experience mostly corresponds to isolated cases and few published series. Objective: To describe the characteristics of IE caused by SL in a multicenter cohort. Method: Prospective cohort study of IE episodes diagnosed in seven hospitals during the years 1984–2012, based on the modified Duke criteria (definite and possible). Demographic data, underlying diseases, underlying heart disease, clinical dates, echocardiographic features, microbiological treatment performed and prognosis. These variables were compared with those caused by other Staphylococcus spp. Results: We diagnosed 17 episodes (1.30%) caused by SL from a total of 1240 episodes of IE. Twelve cases affecting native valves, 2 cases affecting prosthetic valves and 3 cases affecting pacemaker lead. In the sameperiod 188 episodeswere diagnosed caused by other coagulase-negative staphylococci (CoNS) and 265 episodes caused by Staphylococcus aureus (SA). Those caused by SL predominated more in males and had a predominantly community acquisition. These developed heart failure more frequently (59%, 56%, 52%, p = 0.693), severe valvular regurgitation (58%, 38%, 28%, p = 0.020), and needed surgery more often (64%, 53%, 31%, p = 0.001). In contrast, the proportion of patients with severe sepsis was intermediate (23%, 17%, 27%, P = 0.061). Overall mortality was high, similar to those caused by other Staphylococcus spp. (47%, 40%, 46%, p = 0.719). Mortality rate was 18% of the operated and 83% of those receiving medical treatment, although surgery could not be performed in 4 cases due to the patient’s critical situation. Conclusion: Staphylococcus lugdunensis is an uncommon etiology of IE in our cohort, but has serious complications resulting from valve destruction and hemodynamic compromise that requires in most cases, early surgical treatment.