Early transjugular intrahepatic portosystemic shunt (TIPS) used as preventive therapy prior to recurrent bleeding has been recommended in patients presenting with acute esophageal variceal bleeding (EVB) who are at high risk of further bleeding and death. We investigated the impact of early TIPS on outcomes of US patients hospitalized with EVB from 2000 to 2010. The Nationwide Inpatient Sample database was queried to identify patients with EVB and decompensated cirrhosis (because early TIPS is recommended only in high-risk patients). The primary outcome was in-hospital death, and secondary outcomes included rebleeding and hepatic encephalopathy. Early preventive TIPS was defined by placement within 3 days of hospitalization for acute EVB after one session of endoscopic therapy. Rescue TIPS was defined as TIPS after two interventions for EVB. The study included 142 539 patients. From 2000 to 2010, the age-adjusted in-hospital mortality rate decreased 37.2% from 656 per 100 000 to 412 per 100 000 (P <0.01), while early and rescue TIPS increased (0.22% to 0.70%; P < 0.01 and 1.1% to 6.1%; P < 0.01). On multivariate analysis, as compared with no TIPS, early TIPS was associated with decreased inpatient mortality (risk ratio [RR] = 0.87; 95% confidence interval [CI], 0.84-0.90) and rebleeding (RR = 0.56; 95% CI, 0.45-0.71) without an increase in hepatic encephalopathy (RR = 1.01; 95% CI, 0.93-1.11). Early preventive TIPS in patients with EVB and decompensated cirrhosis was associated with significant in-hospital reductions in rebleeding and mortality without a significant increase in encephalopathy in "real-world" US clinical practice. © 2016 Journal of Gastroenterology and Hepatology Foundation and John Wiley & Sons Australia, Ltd.