Ischemic preconditioning (IPC) and intermittent vascular control (IVC) have been shown to reduce the number of ischemia/reperfusion injuries during liver resections with the Pringle maneuver. Our study aimed to compare the beneficial effect of these two modalities in relation to the duration of normothermic liver ischemia. A group of 24 Landrace pigs with a mean body weight of 25 to 30 kg were subjected to extended liver resection of more than 65%. Although, 12 animals underwent IPC (10 minutes of ischemia and 10 minutes of reperfusion), and subsequently the Pringle maneuver was applied for 90 minutes (n= 6) or 120 minutes (n= 6). Another 12 animals underwent liver resection by IVC (20 minutes of ischemia alternated with 5 minutes of reperfusion) for 60 minutes (n = 6) or 120 minutes (n = 6) of inflow vascular control. At 90 minutes of liver ischemia, the IPC group demonstrated lower levels of asportate aminotransferase (AST) (173 +/- 53 vs. 265 +/- 106 IU; p =0.089) and malondialdehyde (MDA) (2.60 +/- 1.03 vs. 5.33 +/- 2.25 micromol/L; p =0.022) and higher liver tissue cAMP (200 +/- 42 vs. 146 +/- 40 pmol/g wet wt, p = 0.04) compared to the IVC group. However, no pathologic differences were observed between the two groups. By contrast, at 120 minutes of liver ischemia, IVC proved to be more beneficial, reflected by lower levels of AST (448 +/- 135 vs. 857 +/- 268 IU; p = 0.006) and MDA (8.33 +/- 1.75 vs. 12.7 +/- 4.31 micromol/L; (p = 0.045), a higher cAMP level (127 +/- 10 vs. 97 +/- 31 pmol/g wet wt p = 0.045), and eventually less cellular necrosis (necrosis score 1.66 +/- 0.51 vs. 2.85 +/- 1.16; p = 0.04) compared to the IPC group. It appears that IPC should be employed when liver ischemia is anticipated to last less than 90 minutes, followed by IVC when the liver ischemia is expected to last 120 minutes.