One-hundred thirty-five (2 to 5 d old) individually fed Holstein heifer calves (38.8 ± 0.62 kg) from 3 commercial dairies were randomly assigned to 1 of 5 milk treatments to evaluate pre- (d 1–42) and post weaning (d 43–56) calf performance and health when fed milk replacers supplemented with a direct-fed microbial (DFM) or neomycin sulfate and oxytetracyline (NT). The study was conducted between June and September 2016. Treatments included 1) all-milk protein, non-medicated milk replacer (MR) 20% CP: 20% Fat fed at 0.28 kg in 2 L of water 2× daily from d 1 to d 35 and 1× daily from d 36 to weaning at d 42, (CON); 2) MR as in CON supplemented with NT at a rate of 22mg/kg BW for 14 d, (MRNT); 3) MR as in CON supplemented with 5 g of DFM containing Bacillus subtilis strain 747 (1 × 10⁹ cfu) per feeding for 42 d, (MRDFM); 4) MR as CON supplemented with 5 g of DFM containing B. subtilis strains 747+1781 (1 × 10⁹ cfu) per feeding for 42 d, (MRDFM2); 5) MR as CON supplemented with 5 g DFM as in MRDFM2 plus Lactobacillus plantarum (5 × 10⁸ cfu) per feeding for 42 d, (MRDFM3). Calf starter (18% CP as fed) and water were fed free choice from d 1 to 56. There were no differences in pre- or postweaning average daily gains (ADG) averaging 0.42 kg/d and 0.88 kg/d respectively. Overall 56 d ADG tended to be greater (P = 0.06) for calves fed MRNT and MRDFM, 0.57 kg/d vs. those fed CON, 0.52 kg/d and MRDFM3, 0.50 kg/d with MRDFM2, 0.54 kg/d being intermediate. Calf starter and MR intake were similar (P > 0.05) across treatments averaging 35.9 and 20.8 kg total intake, respectively. There were no differences in daily fecal scores, scouring days or treatment costs. Under conditions of this study, calves fed milk replacers with MRDFM can perform as well as calves fed MRNT.