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Introduction: Patients leaving against medical advice (AMA) are commonly encountered in hospital medicine. The problem is prevalent worldwide and across all fields of medicine. A retrospective study of 47,583 patients reported a 3.3% AMA rate in 2015., Objectives: In this retrospective study, we aimed (1) to study the demographic, clinical, and laboratory parameters of infective endocarditis (IE) patients leaving AMA. We also compared (2) the various risk factors and outcomes of these patients with IE patients who completed treatment., Results: A total of 111 patients diagnosed with IE were recruited for 36 months. Of the 74 patients with available details, 32 patients (29%) left AMA during their treatment. The mean age of patients leaving AMA was 39, and among those who left AMA, 66% were females. As compared with patients completing therapy, patients leaving AMA tend to have higher comorbidities, including injection drug use (68.1% versus 31.9%), prior IE (83.3% versus 16.7%), and chronic hepatitis C (72.4% versus 27.8%). Rates of consumption of substances of abuse were higher among those who left AMA. Patients leaving AMA also had higher psychiatric comorbidities (63% versus 37.5%), history of leaving AMA (70.5% versus 29.5%), and consumption of more than 2 substances of abuse. Morbidity was higher in patients leaving AMA. There was a statistically significant association between the development of distal embolus ( P < 0.001), the need for recurrent admissions ( P = 0.002), recurrent bacteremia ( P < 0.001), developing new embolus ( P < 0.001), and overall morbidity ( P = 0.002) among IE patients leaving AMA., Conclusions: Infective endocarditis patients leaving AMA tend to be younger females. These patients have prior comorbidities of injection drug use, prior IE, multiple psychiatric comorbidities, drug use, and multiple socioeconomic issues. Patients leaving AMA tend to develop further non-Central nervous system embolic events, recurrent bacteremia, and require frequent admissions. Morbidity in these patients was higher., Competing Interests: The authors disclose no conflict of interest., (Copyright © 2022 Wolters Kluwer Health, Inc. All rights reserved.)