The use of direct-fed microbials in animal nutrition is a growing practice to improve animal health and performance. To investigate the effects of supplementing growing beef heifers with a direct fed microbial (Bacillus coagulans; Provia 6086; Phibro Animal Health Corporation, Quincy, IL), 16 purebred Angus heifers were trained to eat behind Broadbent Calan gates (American Calan, Northwood, NH) during a 28-d acclimation period. Acclimation diet contained a 20:80 concentrate to forage (C:F) ratio. Heifers were assigned to 1 of 2 treatment groups: control (CNTL; n = 8) or direct-fed microbial (Provia 6086 [PV]; n = 8). Three basal diets (40:60, 55:45, and 70:30 C:F ratio) were used in this study: diet 1 (40:60 C:F ratio) was offered on d 1 through 7, diet 2 (55:45 C:F ratio) was offered on d 8 through 14, and diet 3 (70:30 C:F ratio) was offered on d 15 through 28 (of supplementation). Cattle enrolled in the PV group were fed product at the rate of 2 billion cfu/animal per day, hand mixed in the top one-third of the presented diet. Dry matter intake was collected 3 times for diets 1 and 2 and 6 times for diet 3. Body weights were collected at baseline and weekly thereafter; BW were used to calculate ADG, and feed efficiency was calculated as G:F. Serum was collected on d 0, 14, and 28 of supplementation, and samples were assayed for lipopolysaccharide binding protein (LBP), haptoglobin (Hp), and serum amyloid A (SAA). Lipopolysaccharide binding protein, Hp, and SAA were analyzed as change from baseline and log transformed prior to analysis. All data were analyzed using PROC GLIMMIX of SAS; P ≤ 0.05 was considered significant and 0.05 < P ≤ 0.10 was considered trending toward significance. Provia 6086 supplementation improved ADG (P = 0.007; 0.73 kg for CNTL and 1.16 ± 0.10 kg for PV) and feed efficiency (G:F; P = 0.008; 0.08 for CNTL and 0.13 ± 0.03 for PV) compared with control counterparts. Basal diet influenced BW, DMI, G:F, and ADG (P < 0.0001). During diet 1, ADG decreased in all cattle (−0.45 kg/d ± 0.21; P < 0.0001); as a result, compensatory gain was seen during diets 2 and 3. Provia 6086 supplementation had no effect on BW and DMI and had a tendency to increase SAA (P = 0.10) and LBP concentrations (P = 0.05; relative to baseline) when compared with control cattle. This data indicates that providing Provia 6086 during dietary transitions may improve ADG and G:F and modulate the acute phase protein response in growing Angus heifers.