One-hundred three (9 to12 d old) individually fed Holstein heifer calves (41.8 ± 0.66 kg) were randomly assigned to 1 of 4 treatments to evaluate pre- (d 1–35) and post-weaning (d 36 to 49) calf performance and health when fed milk replacers (MR) with alternative protein sources. The study was conducted between April and August, 2014. All calves were fed a common all-milk non-medicated 22% CP:18% fat as-fed MR before the study was initiated. Calves were fed the non-medicated 22% CP:18% fat MR with either (1) All milk protein; (2) 33% of the protein replaced with dried partially hydrolyzed vegetable protein, partially autolyzed yeast and dairy solids; (3) 33% of the protein replaced with a milk extender made from dairy ingredients, edible lard, hydrolyzed vegetable proteins and yeast; or (4) 25% proteins from co-drying cheese and whey by-products. Milk replacers were formulated to be equivalent in lysine and sulfur amino acids. The MR were fed at 0.284 kg in 1.99 L water (12.5% solids) 2× daily from d 1 to 28 and 1× daily from d 29 to weaning at d 35. Calf starter (CS; 18% CP) and water were fed free choice d 1 to 49. During the first 7d of the study, calves were fed 1 part neomycin to 1 part oxytetracycline added to the MR solution to provide 22 mg/kg BW daily. There were no pre- or post weaning ADG differences (P > 0.05). Calves averaged 0.74 kg/d gain for the 49 d study.There were no differences (P > 0.05) in CS or total DMI intake which averaged 53.0 and 69.4 kg for the 49-d study, respectively. There were no differences in pre- and post weaning gain/feed. Gain/feed averaged 0.52 kg for the 49 d study. There were no differences in number of scouring d (d ≥ fecal score 3) pre- and post weaning. Days with fecal scores = 4 were higher (P < 0.05) for Treatment 2 calves vs. those fed Treatments 3 and 4. Health treatment costs did not differ (P > 0.05). Under the conditions of this study, replacing the total milk protein in MR with alternative sources resulted in calf performance and health similar to those fed an all milk protein MR.