This research aimed to evaluate the effects of zilpaterol hydrochloride (ZH; MSD Animal Health, São Paulo, SP, Brazil) on the performance, carcass traits, serum metabolites, body composition, and gain composition of nonimplanted Nellore heifers. Nellore heifers ( = 72; average BW = 267 ± 16 kg; average 18 mo of age) were maintained in a feedlot system for 118 d. Heifers were separated into 2 groups: Control and ZH. The ZH group received ZH (8.3 mg/kg diet DM) for 30 d with 3 d of withdrawal before slaughter. Heifers were allotted to 18 pens, 9 pens per treatment, and assigned to a randomized block design. The animals were weighed, blood samples were collected, and subgroups of heifers were slaughtered at the beginning of supplementation and after 20 and 33 d to evaluate performance, blood metabolites, empty BW (EBW), and EBW composition. Hot carcass and kidney-pelvic fat weights were recorded at slaughter. At 24 h postmortem, carcasses were fabricated and the 9-10-11th rib (HH) section was removed from the primal rib to analyze moisture, protein, ash, and ether extract (EE) content in empty body (EB) and gain composition. Heifers fed ZH had gains in HCW that were 19.7 kg greater than controls, reflecting the 30% increase ( < 0.01) in ADG. There was no change in DMI, resulting in a 20% greater G:F ratio ( < 0.01) for heifers fed ZH. Heifers supplemented with ZH had carcass dressing percentages that were 3% greater than controls ( < 0.01), and there was also a 19% reduction in kidney-pelvic fat ( = 0.05) in ZH-treated heifers. Zilpaterol increased serum creatinine ( < 0.01), tended to increase ( = 0.06) serum triacylglycerol, decreased serum NEFA ( = 0.04), and tended to decrease ( = 0.06) serum glucose. The EBW composition was changed after 20 d of ZH supplementation ( = 0.02), with ZH increasing the moisture, ash, and protein contents, whereas carcass fat was decreased by ZH by 14%. Consequently, the carcass CP:EE ratio after 20 d was increased ( = 0.03) by 24% with ZH supplementation. There was no change on EBW composition after 30 d of ZH supplementation ( = 0.17). Regarding carcass gain composition, ZH increased EBW gain ( = 0.02) by 842 g/d from d 0 to d 30, EB protein gain by 221 g/d ( = 0.05) from d 0 to d 20, and by 180 g/d ( = 0.01) from d 0 to d 33. In conclusion, ZH supplementation in nonimplanted Nellore heifers altered the composition of body weight gain, promoting greater lean tissue deposition and improving feed efficiency.