We postulated that quantitative monitoring of Epstein–Barr virus (EBV) shedding after transplantation could distinguish EBV-associated illnesses and predict clinical outcome. EBV DNA was measured in solid organ (SOT) and hematopoietic cell transplants (HCT) using our own real-time TaqMan EBV PCR. The proportion of patients who had EBV DNAemia post-transplant was significantly lower in HCT vs. SOT (p < 0.001). Over a 7.5-yr period, post-transplant lymphoproliferative disorder (PTLD) occurred in 66 (5.8%) of 1131 patients who met adequate monitoring criteria. SOT recipients developed PTLD significantly later than HCT recipients (median, 2.8 yr vs. 121 d; p < 0.001). PTLD was documented in 53 (14%) of 376 patients who had EBV in ≥1 whole blood sample vs. 13 (2%) of 755 patients who had at least three EBV-negative blood samples and were never positive. PTLD risk in viremic patients increased with the peak quantity of EBV DNAemia (p < 0.001). PTLD occurred in 37/333 (11%) of patients with peak blood levels 103–105 copies/mL vs. 16/43 (37%) of patients with levels >105 (p < 0.001). EBV PCR was predictive in 29 (78%) of 37 patients tested within three wk prior to tissue diagnosis of PTLD, and thus, we conclude that EBV PCR with careful attention paid to changes in EBV DNAemia could lead to earlier diagnosis and treatment of PTLD.