Focal segmental glomerulosclerosis (FSGS) is a relatively prevalent glomerular disorder that often progresses to end-stage renal disease. Thirty to 80% of kidney transplant (KT) recipients with FSGS will experience recurrence characterized by proteinuria and podocyte damage. We hypothesized that the degree of podocyte foot process (FP) effacement in postreperfusion transplant biopsies can be used to predict the development of clinical recurrence of FSGS. Nineteen pairs of pre- and postreperfusion biopsy specimens were studied. We evaluated the degree of FP effacement in postreperfusion KT biopsies by counting the number of widened FP per capillary loop. Early recurrence of FSGS was defined as development of nephrotic range proteinuria between days 3 and 30 posttransplant. Early recurrence occurred in 7 of 19 grafts (36.8%) at a mean of 4.29±1.89 days. The mean score of FP effacement in postreperfusion allograft biopsies was 0.72±0.31 and 1.35±0.63 in the nonrecurrent and recurrent group, respectively (P=0.039). There was an association between FP effacement and proteinuria (P = 0.04). The FP effacement score predicts early recurrence with a sensitivity of 71.4% and specificity of 91.7%. FP effacement can be observed within minutes after reperfusion in renal transplantation of recipients with FSGS that will ultimately develop recurrent FSGS. This suggests a key role for the podocyte injury in the pathogenesis of recurrent FSGS and further supports the presence of circulating factors causing FP effacement. The FP effacement score in the postreperfusion KT biopsy may become a useful predictive test if validated in larger studies.