We have previously documented Caucasian race and cadaver donor source as risk factors for post-transplant lymphoproliferative disorder (PTLD) development in recipients registered in the North American Pediatric Renal Transplant Cooperative Study (NAPRTCS). We analyzed data from the Scientific Registry of the United Network of Organ Sharing (UNOS) (from January 1988 to December 1999) to determine risk factors for the development of PTLD in all organ systems and its frequency, and we compared these factors to the risk factors in the most recent NAPRTCS database (1987–2000). In the UNOS database, PTLD was reported in 2365 of 205 114 organ-transplant recipients (1.2%). PTLD was reported in 3% or more of all intestinal and thoracic organ recipients, but in less than 1% of other abdominal organ recipients. Recipient age < 18 years, Caucasian race and male gender were independent risk factors [Odds Ratios (OR) 2.81, 2.22 and 1.40, respectively, p = 0.0001], but not cadaver donor source. The combination of all three risk factors increased the OR to 8.78. The occurrence of PTLD showed a significant rise per year for heart-lung, kidney, kidney-pancreas and liver transplants, but decreased significantly for heart transplants (p < 0.001). Similar frequencies of PTLD were found in smaller organ-specific registries of heart, intestine, pediatric liver and pediatric kidney transplants. The PTLD incidence per year and incidence density have increased in recent years. Young Caucasian males are at highest risk for PTLD development among solid-organ-transplant recipients. The incidence of PTLD is increasing.