Background: To describe characteristics of sepsis patients who discharged against medical advice (AMA), identify factors associated with AMA discharges in the patients, and evaluate the association of AMA discharge with 30-day unplanned readmission and outcomes of readmission.Methods: Using the National Readmission Database of the United States, we identified inpatients with sepsis who discharged AMA or discharged home between 2010 and 2017. The baseline characteristics were compared between the two groups. Multivariable models were used to identify factors related to AMA discharge, evaluate the association between AMA discharge and 30-day unplanned readmission, and elucidate the relationship between the AMA discharges and in-hospital outcomes.Results: AMA discharges accounted for 2.29% of all the hospitalized sepsis patients. The prevalence of AMA discharge in sepsis patients increased from 1.99% in 2010 to 2.55% in 2014 (p for trend < 0.001).The unplanned 30-day readmission rates of sepsis patients who discharged AMA and who discharged home are 25.51% and 12.26%, respectively. AMA discharge is statistically significantly associated with 30-day [odds ratio (OR), 2.24; 95% confidence interval (CI), 2.15–2.33], 60-day (OR, 2.07; 95% CI, 1.99–2.15), and 90-day (OR, 1.97; 95% CI, 1.90–2.05) readmission. AMA discharge is also associated with longer length of stay in 30 days (0.44 day, 95% CI, 0.12 days-0.76 days, p=0.007), whereas there was no statistically significant difference in hospitalization costs and in-hospital mortality for patients discharged AMA versus those discharged home.Conclusions: Due to the high risk of readmission, vulnerable patients should be early identified. Medical institutions should conduct post-discharge interventions for patients with AMA discharge, such as follow-up visits and psychological counseling, to reduce readmission.