Background: The incidence of infective endocarditis (IE) among people who inject drugs (PWID) is rising worldwide. Multiple clinical guidelines differ on the management of this condition, and few guidelines comment on treatment for primary substance use disorder (SUD). A comprehensive comparison of these guidelines is lacking.Objectives: To perform a critical review identifying key differences in clinical guideline recommendations for treating IE among PWID, focusing on the inclusion of recommendations for SUD treatment and the presence of stigmatizing language.Eligibility Criteria: Recently published, English-language, society-developed clinical guidelines for the treatment of IE among PWID.