Background Vanin-1, an epithelial glycosylphosphatidylolinositol (GPI)-anchored pantetheinase, is a valuable marker of renal injury. Purpose The aim of this study was to assess the predictive value of vanin-1 in acute pyelonephritis (APN) in comparison to the conventional serum inflammatory markers in children aged 1–24 months with the first episode of urinary tract infection (UTI). Material and methods Urinary vanin-1, vanin-1/Cr ratio, WBC, CRP, PCT were analysed in 58 children with febrile UTI and in 18 children with non-febrile UTI. Febrile UTI group was divided into APN subgroup (n = 29) and non-APN subgroup (n = 29), based on the results of Tc-99m-ethylenedicysteine scan. Results The mean vanin-1 level was higher in the APN group compared to the non-febrile UTI group (p = 0.02) and did not differ between APN and non-APN subgroup. In univariate analysis, vanin-1 (p = 0.042), CRP (p < 0.001), PCT (p < 0.001), and WBC (p = 0.022), were associated with APN, but only vanin-1 (p = 0.048) and CRP (p = 0.002) were independent markers of APN. In ROC analysis, vanin-1, with its best cut-off value of 16.53 ng/mL, had worse diagnostic profile (AUC 0.629, sensitivity 58,6%, specificity 63.8%) than CRP, PCT and WBC (AUC: 0.937; 0.880; 0.667, respectively). Conclusions Vanin-1 is not useful for predicting APN, since its diagnostic value is inferior to other conventional serum inflammatory markers.