Background: Interactive response technologies are used in clinical trials to provide services such as automated randomization and medication logistics management. The objective of this article is to investigate the usage of telephone (Interactive Voice Response) and web (Interactive Web Response) interfaces of interactive response technologies at clinical investigator sites in clinical trials, to obtain information about the preferences of interactive response technology end users between the telephone and web interfaces, and to explore the relevance of the telephone interface in this setting. Methods: The data consist of an online survey conducted in spring 2016 with clinical investigators, study nurses, and pharmacists in 13 countries. Results: Ninety-eight percent of survey respondents preferred the web interface over the telephone interface, the most important reason being superior usability. However, the respondents indicated the usability of interactive response technology interfaces is not optimal, and lack of integration and consistency across systems is common. A vast majority of interactive response technology end users at clinical sites prefer to use the web interface over the telephone interface, but most also feel there would need to be a backup system. Conclusions: Based on the results, it would be beneficial to improve the usability of the interactive response technology interfaces, and to increase consistency across systems from the current level. Support to and training of the users, as well as clarifying the responsibilities between sites and the sponsor should also be a focal point. Study sponsors should explore with interactive response technology service providers how removing the telephone interface would impact future studies, and whether there could be a more efficient means to achieve a reliable backup to the web interface instead of a dedicated telephone interface.