Erythrocyte sedimentation rate and C-reactive protein are common preoperative diagnostic markers for prosthetic joint infection but their prognostic role before reimplantation has yet to be defined. We therefore determined the prognostic value of erythrocyte sedimentation rate and C-reactive protein performed before second-stage reimplantation for the treatment of infected total knee arthroplasty (TKA). We studied 109 patients who had undergone two-stage revision TKA for sepsis from 1999 to 2006. Receiver operating characteristic curves were constructed to determine the discriminatory value of erythrocyte sedimentation rate and C-reactive protein before reimplantation in predicting persistent infection. Twenty-three of the 109 patients (21%) required revision surgery for recurrence of prosthetic joint infection. The receiver operating characteristic areas under the curve suggested erythrocyte sedimentation rate and C-reactive protein poorly predicted persistent infection after TKA reimplantation. Cutoff values could not be obtained because of the high variance. We reached similar conclusions regarding the change in erythrocyte sedimentation rate and C-reactive protein levels from time of resection. More accurate diagnostic tools are needed to support clinical judgment in monitoring infection progress and thus deciding whether to proceed with TKA reimplantation. Level of Evidence: Level II, therapeutic study. See Guidelines for Authors for a complete description of levels of evidence.