Severe acute hepatic failure (SAHF), which progresses to fulminant form in some cases, is a life-threatening disease. To assess the technical feasibility and the efficacy of transcatheter arterial steroid injection therapy (TASIT) for SAHF. Twenty-seven patients with SAHF, 10 of whom had variant anatomy of the hepatic artery, underwent radiologic placement of an indwelling catheter in the hepatic artery, and TASIT was subsequently performed for three days. The tips of the catheters were inserted as follows: common hepatic artery (n = 18), proper hepatic artery (n = 4), and replaced right hepatic artery (n = 5). The clinical success rate of TASIT and the prognosis after TASIT were evaluated. In one patient, intimal injury of the left hepatic artery was encountered; however, TASIT could be resumed and completed via intrahepatic arterial collaterals. In two patients, the catheter tip placement was corrected on the following day because of dislocation. Finally, TASIT could be carried out in all patients. Twenty-two patients (81.5%) responded to TASIT but five patients (18.5%) did not. Among the five non-responders, two patients were transferred to liver transplantation and survived, and three patients died. There was no significant difference in the response rates to TASIT among locations of catheter tip (P > 0.05) and extent of drug distribution in the liver (P > 0.05). TASIT is a feasible and efficient treatment option for SAHF regardless of the anatomic variation of the hepatic artery. Careful manipulation during the procedure to prevent injury of the hepatic artery may be the most essential factor not only for successful TASIT but also for liver transplantation, which may be performed on TASIT non-responders.