This study evaluated the effect of a direct-fed microbial (DFM) and its combination with xylanase, amylase, and protease (XAP) enzymes cocktail on performance of broilers, in comparison with two commonly used antimicrobial growth promoters (AGPs). Five treatments were tested using day-old Ross 708 broilers (mixed sex at 50:50 ratio) in a completely randomized design with 8 replications per treatment (40 birds/pen) using built up litter. Treatments were 1) a negative control (NC) based on corn/soy/wheat (10%) containing 500FTU/kg phytase, 2) NC + DFM (150,000 CFU/g of 3 Bacillus strains) (DFM150); 3) NC+ DFM (75,000 CFU/g of 3 Bacillus strains) in combination with XAP, XAP + DFM75); 4) NC+ BMD (50 g/ton), and 5) NC+ virginiamycin (20 g/ton). Diets were fed in mash form ad libitum in 3 phases: d 1 to 10 (starter); d 11 to 21 (grower) and d 22 to 42 (finisher). Body weight and feed intake (FI) were measured per phase and feed conversion ratio (FCR) was corrected for mortality weight. Treatment means were compared using a one-way analysis of variance (ANOVA) and separated via Duncan's Multiple Range Test. Supplementation of DFM increased (P < 0.05) average BW at d 10 when compared to the NC. Overall 42-d data indicated that the combination of XAP+DFM75 reduced (P < 0.05) mortality weight corrected FCR compared to NC, both DFM150 and the combination of XAP+DFM75 did not differ from both AGP treatments. Feed intake and body weight gain (BWG) were not affected by treatments during the 42-d study. The combination of XAP+DFM75 also reduced (P < 0.05) foot-pad lesion score as well as improved energy efficiency compared to the NC. These data indicate that both DFM150 and the combination of XAP + DFM75 may be used as an alternative to AGPs to achieve similar growth performance when producing broilers chickens under similar conditions.