Background: Infective endocarditis (IE) is an important cause of morbidity and mortality. The pattern of the disease in terms of the host, agent and the environment appears to be changing globally. Methods: Patients admitted to a tertiary care center in South India between 2005 and 2015 with definite IE, as confirmed by the modified Duke’s criteria were included in this retrospective analysis. We analyzed the demographic, microbiological and survival data and compared our results with similar studies done in India over the last 3 decades to assess the changing pattern of IE. Results: 172 patients were diagnosed to have definite IE based on modified Duke’s criteria. The mean age of the patients was 41.8 ± 14.2 years, and there was a male predominance (78.4%). Culture positive endocarditis was seen in 83.7 %. Streptococcus species was the predominant etiological agent (44.7%) followed by staphylococcal species (16.8%), enterococcus (9.8%) and gram negative bacteria (9.3%). Native valve endocarditis was seen in 87.8% of patients while prosthetic valve and pacemaker endocarditis was seen in 10.4% and 1.7% respectively. Mitral valve was the most commonly affected valve (52.9%), followed by the aortic valve (23.2%). Multiple valves were involved in 9.3% of patients. Vegetations on the valves were seen in 88.9% of patients. The in-hospital mortality rate was 23.8%. Infection with staphylococcal species, complications of congestive cardiac failure and septic shock were associated with a poor outcome in terms of survival. Conclusion: The disease profile of patients has undergone a change with an increase in mean age and a higher percentage of streptococcal endocarditis. The yield of blood culture has almost doubled over the last three decades. Despite significant advances in medical technology over the last 3 decades, mortality rate remains the same.