BACKGROUND: Population level data on sexual practices, behaviours and health-related outcomes can ensure that responsive, relevant health services are available for all people of all ages. However, while billions of dollars have been invested in attempting to improve sexual and reproductive health (including HIV) outcomes, far less is understood about associated sexual practices and behaviours. Therefore, the World Health Organization embarked on a global consultative process to develop a short survey instrument to assess sexual health practices, behaviours and health outcomes. In order for the resulting draft survey instrument to be published as a 'global' standard instrument, it is important to first determine that the proposed measures are globally comprehensible and applicable. This paper describes a multi-country study protocol to assess the interpretability and comparability of the survey instrument in a number of diverse countries. METHODS: This study will use cognitive interviewing, a qualitative data collection method that uses semi-structured interviews to explore how participants process and respond to survey instruments. We aim to include study sites in up to 20 countries. The study procedures consist of: (1) localizing the instrument using forward and back-translation; (2) using a series of cognitive interviews to understand how participants engage with each survey question; (3) revising the core instrument based on interview findings; and (4) conducting an optional second round of cognitive interviews. Data generated from interviews will be summarised into a predeveloped analysis matrix. The entire process (a 'wave' of data collection) will be completed simultaneously by 5+ countries, with a total of three waves. This stepwise approach facilitates iterative improvements and sharing across countries. DISCUSSION: An important output from this research will be a revised survey instrument, which when subsequently published, can contribute to improving the comparability across contexts of measures of sexual practices, behaviours and health-related outcomes. Site-specific results of the feasibility of conducting this research may help shift perceptions of who and what can be included in sexual health-related research.