Two trials were conducted to evaluate the influence of virginiamycin supplementation on growth performance and digestive function. In trial 1, 144 Holstein steer calves (119 kg of initial BW) were used in a 340-d trial. Treatments were (DM basis) 1) control (no antibiotic); 2) 16 mg/kg of virginiamycin; 3) 22.5 mg/kg of virginiamycin; and 4) 28 mg/kg of monensin. Calves received a steam-flaked corn-based growing diet for the first 112 d and thereafter were fed a finishing diet from d 112 until slaughter. Steers were divided into 2 BW groups (lighter-half and heavier-half), and assigned within groups to 24 pens (6 steers/pen). Virginiamycin did not affect (P > 0.20) ADG, but increased 340-d G:F (linear; P = 0.02) and dietary NE (linear; P = 0.04). Improvements in dietary NE were most pronounced during the final 116 d of the feeding period (linear; P = 0.04) that comprised the hot summer months (June through September). Monensin did not affect (P > 0.20) growth performance or dietary NE. Although average initial BW of the lighter-half and heavier-half BW groups differed by only 4 kg, the heavier BW group had greater HCW (13 kg, P = 0.02), LM area (5.4%, P = 0.01), ADG (4.3%, P = 0.02), G:F (2.3%, P = 0.08), and dietary NE (3.2%. P = 0.01) than the lighter BW group. In trial 2, 4 Holstein steers (269 +/- 3.5 kg) with cannulas in the rumen and proximal duodenum were used in a 4 x 4 Latin square design to evaluate treatment effects on digestion. Virginiamycin did not affect (P > 0.20) ruminal digestion of OM, NDF, starch, and N, and microbial efficiency, but tended to linearly increase (P = 0.09) ruminal N efficiency (nonammonia N flow to the small intestine/N intake). Likewise, virginiamycin did not affect (P > 0.20) postruminal or total tract digestion of OM, starch, NDF, and N. Compared with the control diet, monensin depressed total tract digestion of OM (4.2%, P = 0.03) and NDF (29.5%, P = 0.02). There were no treatment effects (P > 0.20) on ruminal pH, or ruminal lactate and total VFA molar concentration. Virginiamycin increased ruminal molar proportion of acetate (quadratic; P = 0.04) and estimated methane production (quadratic; P = 0.07), and decreased propionate molar proportion (quadratic; P = 0.09). Monensin did not affect (P > 0.20) ruminal VFA molar proportions or estimated methane production. We concluded that virginiamycin supplementation can enhance feedlot growth-performance and dietary energetic efficiency of calf-fed Holstein steers.