OpusXpress is a semi-automated system for high throughput voltage clamp recording from Xenopus oocytes. We participated in the development process for this system and were the only laboratory to field test a prototype. Subsequently, we obtained an early production model that we have used on a regular basis for the last seven years, conducting many thousands of experiments, publishing extensively, and carrying out collaborative research in drug discovery. In this article, we relate our experience with the OpusXpress recording system and large volume oocyte handling. We provide our standard operating procedures and outline the organization of our successful team. Some of our advice is specific to researchers fortunate enough to have access to an OpusXpress system, but most of it is applicable to any group using Xenopus oocytes for the heterologous expression of ion channels.