Background: Acute renal failure (ARF) is not a rare occurrence in severe burns and is an important complication leading to an increase in mortality. The severity of the burn is largely determined by the burn size, and severe burns are likely to cause enough loss of extracellular fluid and albumin from plasma volume to produce shock and hypoalbuminemia. Hypothesis: We hypothesized that initial serum albumin level may be useful as an indicator of prognosis and severity of injury in burned patients. Methods: The clinical characteristics of 147 adult patients with second- and third-degree burns covering 30% or more of their body surface area were analyzed retrospectively. Logistic regression was used to estimate the relative risks of ARF and mortality associated with the larger burn size and the lower serum albumin level at admission. Results: Mean burned body surface was 60.0 ± 21.8% (range 30–100%). Twenty-eight (19.0%) out of 147 patients experienced ARF, defined as a serum creatinine ≧2 mg/dl, during the admission. The patients with ARF had larger burn size (79.5 ± 15.4 vs. 55.3 ± 20.5%, p < 0.0001) and lower serum albumin concentration at admission (1.92 ± 0.66 vs. 2.48 ± 0.82 g/dl, p < 0.0005) compared with those without ARF. All patients with ARF expired, whereas 29.4% (35/119) of the patients without ARF died. The burn size ≧65% was associated with a risk of ARF that was 9.9 times and with a risk of death that was 14.2 times as high as that for the burn size <65%. The initial serum albumin level <2.5 g/dl was associated with a risk of death that was 2.7 times as high as that for the initial serum albumin level ≧2.5 g/dl. Conclusions: When major burns are complicated by ARF, the mortality rate increases significantly. Burn size is an independent predictor of ARF occurring in major burns. Initially depressed serum albumin level is associated with an increase in mortality in the major burn patients.