Background: Damage to a small-for-size liver graft after reperfusion is frequently observed but the mechanism of injury remains unclear. Hypothesis: Injury to a small-for-size liver graft is related to the changes of portal pressure and blood flow. Main Outcome Measures: Survival rates, portal hemodynamics, microcirculatory changes, and morphological changes (by light microscopy and electron microscopy). Setting: A rat model of nonarterialized orthotopic liver transplantation comparing 2 groups of rats transplanted with whole grafts (100% of recipient liver weight) and small-for-size grafts (30% of recipient liver weight). Results: Median survival of the rats with small-for-size grafts was 30 hours (range, 27-37 hours). During the first 15 minutes after reperfusion, mean arterial pressure of the small-for-size graft group was significantly lower than that of the whole graft group (10-minute: 100 vs 132 mm Hg, P=.04; 15-minute: 96 vs 127 mm Hg, P=.04). Portal pressure (in centimeters of water) of the small-for-size graft group was significantly higher in the first 20 minutes after reperfusion than the level before the an hepatic phase (5-minute: 15.1 vs 9.3, P=.02; 10-minute: 16.1 vs 9.3, P=.03: 15-minute, 13.5 vs 9.3, P=.03; 20-minute: 13.4 vs 9.3, P=.03) and was significantly higher than that of the whole graft group in the first 10 minutes after reperfusion (5-minute: 15.1 vs 9.6, P=.02; 10-minute: 16.1 vs 10.3, P=.04). Hepatic microcirculatory blood flow (in milliliters per minute per 100 g) was also significantly higher in the small-for-size graft group during the first 40 minutes after reperfusion (5-minute: 16.3 vs 9.3. P=.02: 10-minute: 14.9 vs 6.6, P=.02; 15-minute: 14.8 vs 5.5, P=.02; 20-minute: 13.1 vs 7.0, P=.02; 30-minute: 13.2 vs 8.8, P=.04; 40-minute: 14.6 vs 7.1, P=.02) Light and electron microscopy showed normal morphological features of whole graft up to 24 hours after reperfusion. The small-for-size graft, however, showed sinusoidal congestion, tremendous swelling of mitochondria of hepatocytes, irregular large gap of sinusoidal lining cells, and collapse of the space of Disse. Conclusions: In a rat model, the portal hemodynamic changes in small-for-size grafts are transient. Progressive damage of the graft may result from microcirculatory failure due to irreversible endothelial injury after reperfusion.