To assess the effect of rituximab therapy and other prognostic factors on overall survival in patients with post-transplant lymphoproliferative disorders (PTLD) after solid organ transplantation, 30 consecutive patients diagnosed with PTLD between 1999 and 2002 were analyzed. Fifteen (50%) patients received rituximab (375 mg/m2 once a week). Fifteen (50%) patients had other interventions including observation, immunosuppression reduction, surgery, chemotherapy, radiation or a combination of these. Patients receiving rituximab vs. non-rituximab differed in the following variables: age at diagnosis of PTLD (P=0.009), days to PTLD (P=0.0005), Epstein-Barr virus (EBV) in situ hybridization status (P=0.02) and CD20-positive status (P=0.006). At the time of last follow-up, 10 (33%) patients in the rituximab group and 5 (17%) in the non-rituximab group were alive. On univariate analysis for overall survival of all 30 patients, the significant factors were: treatment with rituximab (P=0.03), response to treatment (P=0.005), CD20 positive (P=0.0004), low international prognostic index (IPI; P=0.02) and good performance status (P=0.009). Multivariate analysis of all patients was significant for CD20-positive status (P=0.0007) and low performance status (P=0.006). On multivariate analysis for overall survival in patients with CD20-positive PTLD, low IPI (P=0.004) and rituximab therapy (P=0.03) were significant. Low IPI and rituximab therapy led to an improved overall survival in patients with CD20-positive PTLD. © 2005 Taylor & Francis Group Ltd.