Calorie restriction is widely used as a primary therapy for obese pregnant women with gestational diabetes. To better understand the metabolic consequences of marked calorie restriction, we performed a randomized prospective trial under metabolic ward conditions. Obese gestationally diabetic women were randomized to control (n = 5) and calorie-restricted (n = 7) groups. All patients consumed an ∼2400-kcal/day diet during the 1st wk of the study, and at the end of the 1st wk, metabolic features of the two groups were statistically indistinguishable. During the 2nd wk, the control group continued to consume ∼2400 kcal/day, whereas the calorie-restricted group consumed -1200 kcal/day. Twenty-four-hour mean glucose levels remained unchanged in the control group (6.7 ± 0.8 mM wk 1 vs. 6.8 ± 0.8 mM wk 2), although they dropped dramatically in the calorie-restricted group (6.7 ± 1.0 mM wk 1 vs. 5.4 ± 0.5 mM wk 2, P < 0.01). Fasting plasma insulin also declined in the calorierestricted group (265 ± 165 pM wk 1 vs. 145 ± 130 pM wk 2), resulting in a significant change between groups (P < 0.02). Surprisingly, fasting plasma glucose and glucose tolerance measured by the 3-h oral glucose tolerance test did not change within or between groups. Fasting levels of β-hydroxybutyrate rose in the calorie-restricted group (290 ± 240 μM wk 1 vs. 780 ± 30 μM wk 2) but not in the control group (P < 0.01). Finally, urine ketones increased significantly (P < 0.02) in the calorie-restricted group, whereas they remained absent in the control group. We conclude that diets in the range of ∼1200 kcal/day improve glycemic status in obese pregnant women with gestational diabetes but cause significant increases in ketonemia and ketonuria. Because the impact of maternal ketonemia and ketonuria on fetal well-being remains controversial, these changes are of concern. This level of calorie restriction appears unwise for general clinical usage. Further studies are needed to characterize the metabolic consequences of 1600- to 1800-kcal/day diets that have recently been reported to improve glycemic status without causing ketonuria or profound ketonemia.