Abstract Our objective was to evaluate the use of a novel direct-fed microbial as an alternative to antimicrobials to decrease liver abscesses in feedlot cattle. Angus beef steers (n = 240; initial BW = 263 ± 18.0 kg) were used in a randomized complete block design comprised of 3 BW blocks and 3 pen replications per treatment. Experimental treatments were randomly assigned to pen within BW block and consisted of: 1) negative control, dietary supplement contained no tylosin phosphate (NCON); 2) positive control, dietary supplement contained tylosin phosphate (PCON); 3) positive control with tylosin phosphate removed the last 65 d of the feeding period (PCONW); and 4) novel direct-fed microbial fed at 1 g mixture/animal with 1 × 1011 CFU/g (DFM). By design, initial BW did not differ (P = 0.79) among treatments, and at the end of the 59-d receiving period, there were no differences in final BW (P = 0.25). From d 0 to d 30, ADG, DMI, DMI as a percentage of BW, and G:F did not differ (P ≥ 0.21). Likewise, ADG, DMI, DMI as a percentage of BW, and G:F, from d 31 to d 59, were not different (P ≥ 0.30). From d 0 to d 59, there were no differences in ADG, DMI, DMI as a percentage of BW, nor G:F (P ≥ 0.20). During the finishing period, live- and carcass-adjusted final BW did not differ (P ≥ 0.57) among treatments. During the finishing period, there were also no differences in ADG, DMI, DMI as a percentage of BW, or G:F (P ≥ 0.17). Carcass-adjusted ADG, DMI as a percentage of BW, and G:F also did not differ (P ≥ 0.16). Across treatments, no differences in HCW were noted (P = 0.84). Dressing percentage, marbling score, longissimus dorsi (LM) area, 12th-rib fat thickness, and calculated yield grade (YG) were not different among dietary treatments (P ≥ 0.32). Liver abscess incidence and severity were not affected by dietary treatments (P ≥ 0.13). The inclusion of a novel direct-fed microbial in finishing cattle diets did not affect growth performance, carcass characteristics, nor the prevalence of liver abscesses. However, the removal of tylosin phosphate 65 d before harvest numerically resulted in the lowest frequency of severe liver abscesses when compared with steers not fed tylosin phosphate.