The objective of this study was to determine whether increasing corn-based dried distillers grains with solubles (DDGS) in high-barley grain diets reduces the merit of using higher levels of monensin by assessing intake, digestibility, and ruminal pH and fermentation in feedlot heifers. Five ruminally and duodenally cannulated Angus heifers (average BW of 599±36 kg) were used in a 5×5 Latin square with a 2×2+1 factorial arrangement. Treatments were control (CON, 10% barley silage, 90% barley-based concentrate, and 28 mg monensin/kg DM) and diets substituting 20% (LDG) or 40% (HDG) DDGS for barley grain with 28 mg (ML) or 48 mg (MH) monensin/kg diet DM: 1) CONML, 2) LDGML, 3) HDGML, 4) LDGMH, and 5) HDGMH. Contrasts compared LDG vs. HDG, ML vs. MH, interactions between DDGS and monensin, and the effect of increasing DDGS in the diet. Increasing DDGS quadratically (P<0.01) increased DMI. There was no interaction for DMI between the dietary inclusion rate of DDGS and the dose of monensin; however, DMI was reduced (P<0.05) for heifers fed MH vs. ML. Ruminal digestibility of OM, NDF, and starch linearly decreased (P<0.01), but intestinal digestibility linearly increased (P<0.01) with increasing DDGS, resulting in no differences in total tract digestibility. Ruminal digestibility of OM was greater (P<0.04) in heifers fed MH than ML; however, the total tract digestibility of OM was not affected. Intake of N, flows of total N, nonammonia N, and dietary N were linearly (P<0.02) increased, and the efficiency of ruminal microbial synthesis linearly (P<0.04) improved with increasing DDGS. Increasing DDGS inclusion linearly decreased (P<0.04) the acetate to propionate ratio. Inclusion of MH decreased (P<0.04) acetate and increased (P<0.05) NH3-N compared to ML, but high monensin did not affect mean ruminal pH, the duration of pH<5.8, 5.5, 5.2, or the area below the curve at pH 5.8, 5.5, and 5.2, indicating that there was no evidence that it modulated ruminal pH. These results suggest that feeding monensin at 48 vs. 28 mg/kg diet DM altered nutrient availability and site of feed digestion, likely as a result of reduced DMI and increased ruminal digestion of DM. High levels of monensin may reduce the risk of acidosis through a reduction in DMI, but in the present study this was not evident in differences in the ruminal pH profiles between heifers fed ML and MH diets.