Infective endocarditis (IE) is a rare, but life-threatening complication of cardiac device implantation. Despite recent preventive strategies, and advances in antimicrobial and surgical treatment, morbidity and mortality rates are still high.The objective of our study was to assess the epidemiological characteristics, temporal tends and mortality rate of cardiac device related IE (CDRIE) in our high-volume, tertiary referral center.retrospective data collection was performed from January 1, 2006 to December 31, 2016. Thirty-day, 6-month and 1-year mortality was estimated, which were compared to left-sided native valve endocarditis (LSNIE). Patients administered between 2006 and 2010 and between 2011 and 2016 were compared to assess temporal trends.465 cases of IE were administered, out of whom 54 patients had CDRIE (39 males [72%], mean age: 55.8 ±19 yrs; 4 VVI, 7 VDD, 7 VVI-ICD, 20 DDD, 5 DDD-ICD and 11 CRT devices; median time since first implantation: 1558 days [IQR: 470 days – 8.6 yrs]). The infection was caused by streptococci in 3 cases (5.5%), Staphylococci were the most prevalent infective agents (70%), S. aureus (SA) in 28 cases (52%, out of whom 10 were MRSA), coagulase negative Staphylococcus in 10 cases (18.5%), blood culture negative cases in 8 patients (15%), and in 5 cases other pathogens were responsible. 266 patients had LSNIE (201 males [75%], mean age: 54.4 ± 15.6 yrs). There was no difference between the two groups in age or in portion of males. Mortality rates were the same in CDRIE group compared to LSNIE group (30-day: 13% vs 13%, 6-month: 20% vs 25%, 1-year: 26% vs 29% and long-term: 44% vs 44%, ns resp.) Patients who died in the CDRIE group (n = 25) were older (64 yrs [IQR:59-71 yrs] vs 52 yrs [IQR: 27-69 yrs], p = 0.02), male sex was less common (52% vs 79%, p = 0.03), had lower ejection fraction (39.6 ±16.6% vs 54.6 ±14.5%, p < 0.001), had worse renal function (GFR: 46.3 ± 15.3 vs 60.2 ± 23.5 ml/min/1.73m2, p = 0.04), shorter time since first device implantation (2.1 yrs [IQR: 1.1-4.8 yrs] vs 6.7 yrs [4.1-12.9 yrs], p = 0.006), and CRT device implantation were more prevalent (32% vs 10%, p < 0.05).Patients admitted before 2011 (n = 22) did not differ from patients admitted after 2011 (n = 32) in terms of age, male gender, concomitant valve infection, pocket infection, or embolic event. The 30-day (0% vs 6%) and the 1-year mortality (18% vs 31%) were the same before and after 2011, but the 6-month mortality was better before 2011 (4.5% vs 31%, p = 0.01). CRT device implantation was more prevalent over time (5% vs 31%, p = 0.01), and SA infection became more frequent (36% vs 63%, p = 0.05)During the last decade patients with CDRIE had a same survival as patients with LSNIE, every fourth patient died one year after the diagnosis. Almost three-quarter of the infections were caused by Staphylococci, and the portion of S. aureus infection increased over time.