One hundred six (2 to 5 d old) individually fed Holstein heifer calves (39.0 ± 0.63 kg) from 3 commercial dairies were randomly assigned to 1 of 4 milk replacer treatments (MR) supplemented with an organic direct-fed microbial (DFM), neomycin sulfate and oxytetracycline (NT) or combination of (DFM and NT) to evaluate pre- (d 1–42) and post weaning (d 43–56) calf performance and health. The study was conducted between March and June 2017. Treatments included (1) all-milk-protein, non-medicated MR 20% CP:20% fat fed at 0.28 kg in 2 L of water 2x daily from d 1 to d 35 and 1x 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 supplemented with 4 g daily of a DFM containing Bacillus subtilis strain C-3102 (1.2 × 10⁹ cfu/g, d 1–42 ; MRDFM); (4) MR as in MRNT supplemented with DFM as in MRDFM, (MRNTDFM); Calf starter (18% CP as fed) and water were offered free choice from d 1 to 56. Data were analyzed using the mixed procedures of SAS and repeated measures applied where appropriate. There were no differences in pre- (d 1–42), post-weaning (d 43–56), or overall (d 1–56) gains averaging 0.54, 1.00, 0.65 kg/d respectively (P > 0.05). Pre- (d 1–42) and post-weaning (d 43–56) calf starter intake was similar across treatments averaging 16.0 and 26.9 kg total intake. There were no differences in the number of days fecal scores were 3 ≥ (d 1–42, 1 = normal, 4 = watery) averaging 1.23, 1.11, 1.49, and 1.63 d, respectively (P > 0.05). Fecal sample analyses from a subset of calves on each treatment showed no difference (P > 0.05) in Enterobacteriaceae levels across treatments. Health costs were similar across treatments. Under conditions of this study, calves fed a MR supplemented with a DFM, NT or combination of DFM and NT did not affect growth or health costs compared with calves fed a non-medicated MR.