Prior research suggests that cross-national cognitive interviewing can provide preliminarily insights into the extent to which survey items that will be employed in large-scale global research might be understood similarly or differently across countries. Against the backdrop of the recently launched Global Flourishing Study, we used multinational cognitive interview data from 116 individuals (M = 41.4 years, SD = 14.9, female = 50.9%) in 22 countries to explore similarities and differences in item difficulty and comprehension of five of the Global Flourishing Study survey items that are related to personal wellbeing. Interviewer observations indicated that most participants (≥ 90%) did not experience a lot of difficulty responding to each of the items. Focusing on a specific comprehension probe that was common across the five items (i.e., “In your own words, what is this question asking?”), we applied the constant comparative analytic method to generate an overarching theme for each item that captured the common core or essence of how participants across the countries interpreted the items. However, there was some variability—both between and within countries—in how responses to the probe in the different countries related to the overarching theme for each item. Given the richness of the Global Flourishing Study as a possible data resource, including its broad representativeness of the global population and availability as an open access dataset, these findings will be useful to researchers who are interested in using data from the Global Flourishing Study to study human wellbeing in different parts of the world.