Nonalcoholic fatty liver disease (NAFLD) is very prevalent in obese patients. However, increases in serum aminotransferase levels after weight loss have raised clinical concerns. This study documented sequential changes of serum aminotransferase levels for severely obese patients who lost a substantial amount of weight in a behavioral weight loss program. One hundred three severely obese patients who lost > 45.5 kg were treated in our clinic's weight management program. The prevalence of all risk factors except diabetes was higher among those with elevated (AE) baseline serum alanine transferase (ALT) levels than those with normal levels (AN). Weight losses at 8 and 24 weeks were 19.8 and 43.5 kg in the AN group (n = 79 patients) and 21.8 and 45.5 kg in the AE group (n = 24 patients), respectively. Total weight losses after completion of the program were 58.4 kg in the AN group and 57.6 kg in the AE group. The baseline levels for the AN group were: ALT, 25.4 U/L and aspartate aminotransferase (AST)/ALT ratio, 0.87. The baseline levels for the AE group were: ALT, 68.0 U/L and AST/ALT ratio, 0.61. Peak ALT levels were 75.4 U/L in the AN group and 94.0 U/L in the AE group. The final serum ALT levels were 23.7 U/L and 27.3 U/L in the AN and AE groups, respectively. This severely obese population had a very high frequency of ALT elevations with weight loss, but elevations were transient; values usually returned to below baseline levels after substantial weight loss.