Background: Patients who leave hospital against medical advice (AMA) may be at risk of adverse health outcomes, medical complications, and readmission. In this study, we examined the characteristics of patients who left AMA after traumatic brain injury (TBI), their rates of follow-up visits, and readmission. Methods: We retrospectively studied 106 consecutive patients who left the tertiary trauma center AMA (1.8% of all admitted patients with a TBI). Preinjury health and social issues, mechanism of injury, computed tomography findings, and injury markers were collected. They were correlated to compliance with follow-up visits and unplanned emergency room (ER) visits and readmission rates. Results: The most prevalent premorbid health or social-related issues were alcohol abuse (33%) and assault as a mechanism of trauma (33%). Only 15 (14.2%) subjects came to follow-up visit for their TBI. Sixteen (15.1%) of the 106 subjects had multiple readmissions and/or ER visits related to substance abuse. Seven (6.6%) had multiple readmissions or ER visits with psychiatric reasons. Those patients with multiple readmissions and ER visits showed in higher proportion preexisting neurological condition (p=0.027), homelessness (p=0.012), previous neurosurgery (p=0.014), preexisting encephalomalacia (p=0.011), and had a higher ISS score (p=0.014) than those who were not readmitted multiple times. Conclusions: The significantly increased risks of multiple follow-up visits and readmission among TBI patients who leave hospital AMA are related to a premorbid vulnerability and psychosocial issues. Clinicians should target AMA TBI patients with premorbid vulnerability for discharge transition interventions.