The welfare of transgenic animals is often not considered prior to their generation. However, we demonstrate here how a welfare risk assessment can be carried out before transgenic animals are created. We describe a risk assessment identifying potential welfare problems in transgenic pigs generated for future xeno-donation of organs. This assessment is based on currently available information concerning transgenic animal models in which one or more transgenes relevant to future xeno-donation have been inserted. The welfare risk assessment reveals that future xeno-donor pigs may have an increased tendency toward septicaemias, reduced fertility and/or impaired vision. The transgenic animal models used in generating hypotheses about the welfare of xeno-donor pigs can also assist in the testing of these hypotheses. To ensure high levels of welfare of transgenic animals, analogous risk assessments can be used to identify potential welfare problems during the early stages of the generation of new transgenic animals. Such assessments may form part of the basis on which licenses to generate new transgenic animals are granted to research groups.