A trend toward international multicenter clinical trials in the medical device industry is helping to increase recruitment figures and to improve the generalizability of results, among other factors. However, working globally creates its own unique set of problems, which are rarely discussed in the literature. This article considers these issues from multicenter, multicultural, and multilingual perspectives. A multicenter study implies a replication of work to coordinate research sites that are working under different regulations. Standardizing elements of the clinical trial is essential for proper comparison of results. Multicultural differences manifest themselves in different forms in international clinical research. However, the impact of culture on a study's success is a real issue, particularly when patient-reported outcomes form part of the trial. A trial that is conducted globally obviously requires the use of local language material, but this element is fraught with the possibility of mistranslation and misunderstanding. In this article, we also examine the composition of a research team and how to keep everyone involved in a global clinical trial both informed and enthused about a trial that may last several years. Examples from our own clinical investigations are reported throughout this article.