This is a case report of three patients who were managed for right sided infective endocarditis, each posing diagnostic challenges due to atypical clinical presentations and negative blood culture results. Case 1 is a 20-year-old female intravenous (IV) drug user who presented with septic emboli to the lung. Case 2 is a 43-year-old woman with a tunnel catheter for dialysis who had huge vegetations on the tricuspid valve which turned out to be fungal in origin. Case 3 is a 45-year-old female with background Ehlers-Danlos syndrome who developed tricuspid endocarditis following IV injections/line in a peripheral hospital. In this report, we discussed the factors causing late diagnosis of isolated tricuspid valve infective endocarditis in our environment, challenges of diagnosing this condition in patients with underlying health issues and the difficulties of obtaining blood culture results.