One-hundred 34 (2 to 5 d old) individually fed Holstein heifer calves (38.6 ± 0.63 kg) from 3 commercial dairies were randomly assigned to 1 of 5 milk replacer treatments (MR) supplemented with direct-fed microbials (DFM) or neomycin sulfate and oxytetracycline (NT) to evaluate pre- (d 1–42) and post weaning (d 43–56) calf performance and health. The study was conducted between December and February 2017. Treatments included (1) all-milk protein, non-medicated 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 22 mg/kg BW/d for 14 d, (MRNT); (3) MR as in CON with a DFM containing Lactobacillus acidophilus NP51 and Propionibacterium freudenreichii NP24 included in the MR providing 0.5 g/d, (MRDFM1); (4) MR as in CON with a DFM containing multiple Bacillus subtilis strains (5 × 10⁹ cfu/g) included in the MR providing 1.0 g/d (MRDFM2); (5) MR as in CON supplemented with 5 g per feeding of a DFM containing a single Bacillus subtilis strain (5.0 × 10⁹ cfu/g; MRDFM3); Calf starter (18% CP as fed) and water were offered free choice from d 1 to 56. Data were analyzed using the PROC mixed procedures of SAS and repeated measures analyses applied where appropriate. There were no differences in pre-weaning (d 1–42), post-weaning (d 43–56), and overall (d 1–56) gains averaging 0.59, 1.12, and 0.72 kg/d respectively (P > 0.05). Pre-weaning (d 1–42) and post-weaning (d 43–56) calf starter intake was similar across treatments averaging 21.2 and 32.8 kg total intake, respectively. There were no differences in gain/feed, hip height gain, daily fecal scores, or health costs (P > 0.05). The number of days fecal scores were 3 ≥ (d 1–42, 1 = normal, 4 = very loose, watery) were similar across treatments averaging 3.04, 2.56, 2.48, 3.01, and 2.64 d respectively (P > 0.05). Under conditions of this study, calves fed a MR supplemented with a DFM or NT in MR did not improve growth, fecal scores or health costs compared with calves fed a non-medicated MR.