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Background.  The clinical significance and appropriate management of graft pyelonephritis diagnosed by biopsy are poorly understood. Methods.  We analyzed data from all patients with pyelonephritis on transplant kidney biopsy from January 1998 to December 2019. Patients were divided into 2 groups: those whose urinalysis was positive for urinary tract infection (UA+) and those whose urinalysis was negative (UA–). Results.  There were a total of 101 patients with the diagnosis of pyelonephritis by biopsy during the study period. The mean time from transplant to pyelonephritis diagnosis was 3.3 ± 4 y. Thirty-six (35.6%) of the patients with pyelonephritis on biopsy had a negative UA. Out of 65 patients in the UA+ group, 54 (83%) received antibiotics. Only 12 of the UA– patients (33%) received antibiotics. The use of antibiotics in both the UA+ (P = 0.03) and UA– groups (P = 0.02) compared with no use of antibiotics was associated with better death-censored graft survival. On multivariate analysis, the use of antibiotics (hazard ratio = 0.22, P = 0.001, 95% confidence interval, 0.12-0.61) was associated with improved graft survival. Conclusion.  The finding of pyelonephritis on a transplant kidney biopsy is almost always a surprise but is an important finding. Treatment with antibiotics, regardless of signs or symptoms of urinary tract infection, is associated with improved graft survival.