HLA-specific antibodies (HSA) and soluble CD30 (sCD30) were measured in 208 renal transplant recipients with functioning grafts at least 1 year after transplantation (median 8.2 years) to investigate the predictive value of HSA and sCD30 on subsequent graft outcome. HSA (class I and class II) were detected by both ELISA LAT-M and Luminex LabScreen assays. Data on graft outcome was collected with a median follow-up time of 3.5 years after antibody and sCD30 measurement. Recipients with post-transplant HLA class II antibodies had particularly poor graft outcome with a hazard ratio (HR) of 7.8 (p <0.0001) when detected by ELISA, and a HR of 6.0 (p <0.0001) when detected by Luminex. A high post-transplant sCD30 level >= 100 U/mL was associated with increased risk of subsequent graft failure (HR 2.7, p = 0.03). sCD30 and HSA had an independent and additive association with graft outcome. Recipients with HLA class II antibody and high sCD30 had the highest risk of subsequent graft failure (HR 43.4, p <0.0001 and HR 18.1, p = 0.0008 for ELISA and Luminex, respectively). These data show that detection of HSA and serum sCD30 measured at least 1-year post-transplant provides valuable and predictive information regarding subsequent graft outcome.