Aim: To assess the short- and long-term effects of transjugular intrahepatic portosystemic shunt (TIPS) on hepatic and systemic hemodynamics, on gastroesophageal collateral flow, and on hepatic, renal, and cerebral function in patients with liver cirrhosis. Patients and methods: At baseline and after elective TIPS implantation, a total of 122 patients with cirrhosis and recurrent variceal bleeding or refractory ascites was prospectively investigated and compared to the results of corresponding age- and sex-matched controls. Before and at fixed time points after TIPS insertion routine clinical, laboratory, and color Doppler ultrasonography parameters were assessed. Parameters of the systemic hemodynamics were determined using a Swan-Ganz catheter and the hepatovenous pressure gradient and the gastroesophageal collateral flow were examined after catheterization of the hepatic vein and the azygos vein, respectively. Liver function was quantified by a panel of five tests measuring microsomal and cytosolic function and liver blood flow. The glomerular filtration rate and renal plasma flow were determined by inulin- and p-aminohippurate clearances, respectively. In addition, the activity of vasoactive humoral systems was measured. To assess manifest and subclinical encephalopathy various psychometric tests and the latencies of visual endogenous event-related (VEP) N250 and P300 potentials were used. Results: 1) TIPS was successfully inserted in all patients and led to an immediate and long-term reduction of the hepatic-venous pressure gradient. 2) TIPS implantation led to an immediate but only transient aggravation of the hyperkinetic circulation in patients with liver cirrhosis. 3) After 1 year, parameters of the systemic hemodynamics have returned to baseline levels. 4) In contrast, the reduction of blood flow through gastroesophageal collaterals was delayed and not complete before 1 year after TIPS. 5) In contrast to endoscopic therapy, TIPS placement was followed by an immediate and sustained decrease in hepatic blood flow and cytosolic and microsomal liver function. 6) These changes were significantly more obvious in patients with compensated cirrhosis (Child classification A and B) compared to patients with advanced cirrhosis (Child classification C). 7) TIPS implantation reduced the activity of the renin-angiotensin-aldosterone and sympathetic nervous system in both patients with refractory ascites and in patients without ascites. 8) TIPS improved renal function and renal blood flow. 10) TIPS insertion deteriorated cerebral functions and, in contrast to endoscopic therapy, increased the risk for the development of subclinical hepatic encephalopathy and led to significant more episodes of overt hepatic encephalopathy. 11) Chronic hepatic encephalopathy was not observed after TIPS. 12) Univariate analysis identified hepatic encephalopathy in history, Child-Pugh score, serum sodium, bilirubin, age, stent diameter and the N250- and P300-latencies at baseline as risk factors for developing overt hepatic encephalopathy after TIPS. 13) In multivariate analysis, only hepatic encephalopathy in history and low serum sodium concentrations before TIPS turned out as significant predictors for post TIPS hepatic encephalopathy. Conclusions: 1) TIPS does not seem to cause long-term aggravation of the hyperkinetic circulation in patients with liver cirrhosis. 2) The procedure significantly deteriorates the underlying hyperdynamic syndrome immediately after TIPS. Therefore, myocardial and pulmonal performance should be explored before TIPS. 3) The procedure should be considered with caution in patients with limited cardiac reserve. 4) TIPS might accelerate the course of cirrhosis by reduction of the lover blood flow and hepatic function. 5) Obviously, cirrhotic livers with preserved metabolic function and regenerative capacity seem to be more sensitive to reductions of portal perfusion and, thus, potential loss of trophic factors than organs with advanced cirrhosis where sinusoidal perfusion with portal blood is largely dried up. 6) TIPS represents a secondary rather than a first line tool for the treatment of variceal hemorrhage and refractory ascites. 7) Improvement of renal function and reduction in the activities of the renin-angiotensin-aldosterone and sympathetic nervous system in both patients with refractory and without ascites occur independent of changes in systemic and peripheral hemodynamics as well as renal vascular resistance. 8) A history of overt hepatic encephalopathy and a serum sodium concentration below 132 mmol/L might be useful parameters to identify patients in whom TIPS should not be performed.