Fifteen Holstein cows (10 multiparous and 5 primiparous) in early to mid lactation (79.3 +/- 9.2 d in milk) were used in a multiple 5 x 5 Latin square design with 4-wk periods to evaluate and compare the use of condensed corn distillers solubles (CCDS) and dried distillers grains with solubles (DDGS) in the total mixed ration. The forage portion of the diets was kept constant at 27.5% corn silage and 27.5% alfalfa hay (dry matter basis). Diets were 1) 0% distillers grains products (control); 2) 18.5% DDGS; 3) 10% CCDS; 4) 20% CCDS; and 5) a combination diet of 18.5% DDGS with 10% CCDS. Diets 2 and 3 contained 2% fat from DDGS or CCDS, whereas diet 4 contained 4% fat from CCDS and diet 5 contained 4% fat from the blend of DDGS and CCDS. The diets were balanced to provide 17% crude protein with variation in acid detergent fiber, neutral detergent fiber, and fat concentration. Dry matter intake (21.5 kg/d) was similar for all diets. Milk yield (33.8, 36.2, 35.5, 36.0, and 36.0 kg/d) tended to be greater for diets 2 to 5 than for diet 1, whereas yields of fat (1.04 kg/d), protein (1.02 kg/d), fat percentage (2.94), and protein percentage (2.98) were similar for all diets. Energy-corrected milk (32.2 kg/d) and feed efficiency (1.58 kg of energy-corrected milk/kg of dry matter intake) were similar for all diets. Milk urea nitrogen (15.0, 10.9, 11.1, 11.0, and 11.4 mg/dL) as well as blood urea nitrogen (15.6, 12.5, 14.6, 13.8, and 14.2 mg/dL) were decreased in diets 2 to 5 compared with diet 1. Milk concentrations of long-chain fatty acids as well as polyunsaturated fatty acids were greater and medium-chain fatty acid concentrations were lower for diets 2 to 5 compared with diet 1. Concentrations of cis-9, trans-11 conjugated linoleic acid (CLA; 0.33, 0.68, 0.51, 0.85, and 1.07 g/100 g of fatty acids) as well as trans-10, cis-12 CLA (<0.01, 0.01, <0.01, 0.02, and 0.02 g/100 g of fatty acids) were greater for diets 2 to 5 compared with diet 1. Molar proportions of ruminal acetate decreased and propionate increased for diets 2 to 5 compared with diet 1. The results showed that CCDS is as effective as DDGS in replacing soybean meal and corn grain in the total mixed ration.