The prophylactic use of oral antimicrobials is common practice in calf rearing, however, the impacts on gut health are largely unknown. The objective of this study was to investigate the effects of oral antibiotic (neomycin) on calf health, performance, and gastrointestinal development. One hundred fifty calves, less than a week old, were blocked by BW and randomly assigned to 1 of 3 treatments (n = 50 per treatment): control (CON: non-medicated milk replacer; MR), short-term antibiotic (ST: neomycin mixed in MR at 20mg/kg BW from d1–14), or long-term antibiotic (LT: neomycin in MR at 20mg/kg BW from d1–28). Fecal dry matter and BW were measured weekly, whereas daily fecal scores (FS) were assigned for the first 28 d. Data were analyzed using the mixed procedure of SAS. Fixed effects included treatment, period, day, and their interactions, and the random effect of calf within treatment. Statistical significance was considered at P ≤ 0.05. A treatment effect (P = 0.01) was observed for FS, where CON calves experienced higher average FS (0.640 ± 0.031) compared with ST (0.530 ± 0.034) and LT calves (0.409 ± 0.034). CON calves also experienced longer bouts (P < 0.01) of diarrhea (5.44 ± 0.35 d) compared with ST (3.78 ± 0.39 d) and LT calves (3.82 ± 0.38 d). At d7, significant differences were observed in fecal dry matter (P < 0.01), where CON calves experienced lower fecal dry matter (0.130 ± 0.012%) than ST (0.200 ± 0.013%) or LT (0.170 ± 0.013%) calves. No significant differences in average daily gain (P = 0.475; SEM = 0.0546) were observed. On d 28, a subset of 36 calves (n = 12 per treatment) were euthanized and dissected to assess gastrointestinal development. Histomorphometric measurements were characterized in the distal jejunum, ileum, and colon. Calves in the LT group had heavier (27.50 ± 2.58 g) duodenums (P = 0.04) and deeper (515.58 ± 6.31 μm) distal jejunum crypt depths (P < 0.001). The results of this study suggest that while neomycin may affect intestinal morphology and decrease the incidence and severity of diarrhea, it has no effect on growth performance, which questions the efficacy of neomycin inclusion in milk replacer.