Non-typeable Haemophilus influenzae (NTHI) rarely cause endocarditis. Of the limited reports of H influenzae endocarditis, most have been due to encapsulated organisms or have had limited bacterial characterisation. We encountered a transplant recipient with native valve NTHI endocarditis and were intrigued to find no previous descriptions of this entity. Although it was tempting to ascribe this infection to our patient's immunocompromised status, we investigated his pathogen further and found that it displayed features common to invasive NTHI strains including gene expression for two IgA proteases and serum resistance. Multilocus sequence typing grouped our NTHI strain with MLST 159, a group associated with invasive NTHI infections. Our strain shared identical outer membrane protein P2 sequences and protein patterns with MLST 159 strains. Aside from providing the first characterisation of native valve NTHI infection, our investigation reveals features of epidemiologically unrelated, clonal NTHI strains that have a predilection for invasive infections.