OBJECTIVE The accurate preoperative diagnosis of infected tibial nonunion remains challenging. Hence, we evaluated the diagnostic potential of novel biomarkers for infected tibial nonunion. METHODS This single-center retrospective study was conducted in 252 patients divided into two groups: infected tibial nonunion (67 patients) and aseptic tibial nonunion (185 patients). The preoperative clinical biomarkers included D-dimer, fibrinogen, albumin, globulin, total protein, and C-reactive protein (CRP) levels; albumin-to-globulin ratio (AGR); erythrocyte sedimentation rate (ESR); and white blood cell (WBC) count. Receiver operating characteristic (ROC) curves, sensitivity, and specificity were utilized to compare the biomarkers' diagnostic potential. RESULTS The area under the curve (AUC) values for fibrinogen and AGR were 0.829 and 0.821, respectively, suggesting similarly good diagnostic potentials for infected tibial nonunion. Fibrinogen and AGR were better diagnostic biomarkers for infected tibial nonunion than the WBC count; ESR; D-dimer, albumin, globulin, CRP, and total protein levels, whose AUC values were 0.623, 0.684, 0.741, 0.797, 0.765, 0.715, and 0.554, respectively. The sensitivity and specificity of fibrinogen with a cut-off value of 3.35 g/L were 71.64% and 84.86%, respectively. The corresponding values for AGR with a cut-off value of 1.33 were 73.13% and 86.49%. Moreover, the fibrinogen-AGR (FAGR), i.e., the combination of fibrinogen and AGR, had the highest diagnostic accuracy for infected tibial nonunion (AUC = 0.906). The optimal FAGR cut-off was 2.69, with fair sensitivity (74.63%) but the highest specificity (94.59%). CONCLUSIONS Fibrinogen, AGR, and FAGR are promising biomarkers for the diagnosis of infected tibial nonunion.