The objective of this study was to determine if a higher-fiber diet alters the response of finishing pigs to an antimicrobial (tylosin phosphate [TP]) and a nutrient partitioning agent (ractopamine HCl [RAC]) in terms of N and water utilization and energy digestibility. Seventy-two gilts (initial BW = 107.4 ± 4.2 kg) were blocked by weight and allotted to 1 of 8 dietary treatments. Treatments were arranged as a 2 × 2 × 2 factorial: distillers dried grains with solubles (DDGS; 0 vs. 30%), RAC (0 mg of RAC/kg and 0.70% standardized ileal digestible [SID] Lys vs. 5 mg of RAC/kg and 0.95% SID Lys) and TP (0 vs. 44 mg of TP/kg). Pig was the experimental unit, with 9 replications per treatment. Pigs were housed in individual metabolism crates and fed treatment diets for 17 d. Feed was provided twice daily, as much as the pigs could consume within 1 h per meal, and water was provided to the pigs between feeding periods, ad libitum. Fecal and urine collection occurred on d 7 and 8 and on d 15 and 16, for sampling periods 1 and 2, respectively. Pigs fed the DDGS diets had reduced ADG ( < 0.001) and ADFI ( < 0.0001). The apparent total tract digestibility (ATTD) of N and GE were lower for the 30% DDGS diets than the 0% DDGS diets ( < 0.0001). Ractopamine improved ADG ( < 0.0001), G:F ( < 0.0001), and N retention ( < 0.001) and tended to increase daily water intake ( < 0.10). Pigs fed RAC had higher N intake and urinary excretion and lower N retention in Period 2 than in Period 1 ( < 0.05), indicating a decline in the response to RAC over time. Tylosin phosphate did not affect ADFI or G:F but did improve ATTD of N ( < 0.05). There was a tendency for a TP × DDGS interaction ( < 0.10) for ADG, where TP tended to increase ADG in pigs fed 0% DDGS diets ( < 0.10) but not in pigs fed 30% DDGS diets ( > 0.10). Pigs fed DDGS diets had higher N intake ( < 0.01) and higher fecal ( < 0.0001) and urinary ( < 0.01) N excretion with no difference in N retention (g/d). Overall, RAC increased N retention by 33% ( < 0.0001) and the response to RAC was similar in both corn-soybean meal-based and corn-soybean meal-DDGS-based diets. Tylosin phosphate tended to improve growth performance in pigs fed corn-soybean meal-based diets but not in diets containing 30% DDGS; however, this response was not explained by changes in N balance or in energy digestibility.