Management of complicated massive infective endocarditis (IE) in patients who are contraindicated for surgical valve replacement has long been a dilemma for many clinicians. Studies have shown that massive IE patients who were treated conservatively generally result in poorer prognosis. We report two cases of massive native valve infective endocarditis with severe mitral valve regurgitation and septic emboli that has been successfully treated conservatively. Interestingly, despite having a large vegetation and multiple septic emboli complications, none of these two cases had any positive culture or serology. Managing culture negative IE without surgical intervention pose an even greater challenge to the choice and duration of antibiotics with further long-term plans. We hope to share these case series to aid in the management dilemma of similar cases in the future.