Dried distillers grains with solubles (DDGS) has become more nutritionally consistent as the industry has evolved. The objective of this study, therefore, was to evaluate the feed efficiency of lactating Holstein dairy cattle fed 2 different concentrations of DDGS. Thirty cows were fed 0, 10, and 20% DDGS dietary dry matter (DM) as a total mixed ration. Cows were stratified by parity and days in milk into 3 treatment groups of 10 cows in a 3 × 3 Latin square with repeated measures. We hypothesized that feeding 20% DDGS by dietary DM would negatively influence production and efficiency. Feeding DDGS had no consistent effect on dry matter intake (DMI), with the control diet being intermediate to the 10 and 20% diets (25.22, 24.03, and 26.37 kg/day, respectively; P < 0.0001). Milk yield was unaffected by feeding DDGS; feeding DDGS, however, caused milk fat depression (3.45, 2.94, and 2.68%; 0, 10, and 20%, respectively; P < 0.0001) and reduction of daily fat yield (1.35, 1.15, 1.04 kg/day; P < 0.0001) that resulted in decreases in 3.5% fat-corrected milk (FCM) yield (36.20, 32.97, and 31.32 kg/day; P < 0.0001) and energy-corrected milk (ECM) yield (40.95, 38.12, and 36.72 kg/day; P < 0.0001). Both protein (3.58, 3.62, and 3.65%; P = 0.0409) and lactose percentage (5.07, 5.15, and 5.17%; P = 0.0067) were increased when cows were fed 20% DDGS; neither protein nor lactose yield, however, was affected. Protein efficiency decreased for cows fed 20% DDGS (35.42, 36.21, and 32.76%; P < 0.0001), likely resulting from heat-damaged protein. All measures of energetic efficiency [ECM/DMI, kg ECM/net energy for lactation (NE_L) intake (mcal), and gross energy (GE) of milk produced (mcal)/NE_L caloric intake (mcal)] were decreased when cows were fed 20% DDGS, but not when cows were fed 10% DDGS (ECM/DMI: 1.66, 1.64, and 1.41; kg ECM/NE_L: 1.02, 1.03, 0.89; GE of milk/NE_L caloric intake: 0.65, 0.66, 0.56; P < 0.0001). These results indicate that, with the exception of an approximate 0.5% loss of milk fat, the DDGS used in this study can be effectively fed at 10%, but not at 20%, of dietary DM without a loss in feed efficiency.