Information describing the incidence and clinical characteristics of late infection (LI) in solid organ transplantation (SOT) is scarce. The aim of this study was to define the incidence, clinical characteristics and risk factors for LI (>6 months) as compared with infection in the early period (<6 months) after SOT. By the online database of the Spanish Network of Infection in Transplantation (RESITRA) we prospectively analyzed 2702 SOT recipients from September 2003 to February 2005. Univariate and multivariate analysis using logistic regression were performed to calculate the risk factors associated with the development of LI. A total of 131 patients developed 176 LI episodes (8%). Global incidence of LI was 0.4 per 1000 transplant-days, ranging from 0.3/1000 in kidney transplants to 1.4 in lung transplants. Independent risk factors for LI in were: acute rejection in the early period (OR 1.5; CI 95%: 1.1–2.3), chronic graft malfunction (OR 2; CI 95%: 1.4–3), re-operation (OR 1.9; CI 95%: 1.3–2.8) relapsing viral infection apart from CMV (OR 1.9; CI 95%: 1.1–3.5), previous bacterial infection (OR 1.8; CI 95%: 1.2–2.6) and lung transplantation (OR 4.5; CI 95%: 2.6–7.8). Severe LI occurs in a subgroup of high-risk SOT recipients who deserve a more careful follow-up and could benefit from prolonged prophylactic measures similar to that performed in the early period after transplantation.