Background. Whether antibiotic treatment of asymptomatic bacteriuria (AB) can prevent acute graft pyelonephritis (AGP) in kidney transplant (KT) recipients has not been elucidated. Methods. In this multicenter, open-label, nonblinded, prospective, noninferiority, randomized controlled trial, we compared antibiotic treatment with no treatment for AB in KT recipients in the first year after transplantation when urinary catheters had been removed. The primary endpoint was the occurrence of AGP. Secondary endpoints included bacteremic AGP, cystitis, susceptibility of urine isolates, graft rejection, graft function, graft loss, opportunistic infections, need for hospitalization, and mortality. Results. We enrolled 205 KT recipients between 2013 and 2015. AB occurred in 41 (42.3%) and 46 (50.5%) patients in the treatment and no treatment groups, respectively. There were no differences in the primary endpoint in the intention-to-treat population (12.2% [5 of 41] in the treatment group vs 8.7% [4 of 46] in the no treatment group; risk ratio, 1.40; 95% confidence interval, 0.40-4.87) or the per-protocol population (13.8% [4 of 29] in the treatment group vs 6.7% [3 of 45] in the no treatment group; risk ratio, 2.07, 95% confidence interval, 0.50-8.58). No differences were found in secondary endpoints, except for antibiotic susceptibility. Fosfomycin (P =.030), amoxicillin-clavulanic (P <.001) resistance, and extended-spectrum beta-lactamase production (P =.044) were more common in KT recipients receiving antibiotic treatment for AB. Conclusions. Antibiotic treatment of AB was not useful to prevent AGP in KT recipients and may increase antibiotic resistance. However, our findings should be regarded with caution, due to the small sample size analyzed.