Background: Previous studies evaluating the cultural and structural factors underpinning the large variations in the consumption of antibiotics in high-income countries have reached different conclusions. Some studies have found that corruption plays a dominant role, whereas other studies have concluded that cultural factors such as the degree of uncertainty avoidance (UA) and performance-orientation versus cooperation-orientation (POCO) are more important. These studies have been limited to Europe, and we, therefore, aimed to expand this analysis to all high-income countries with available data. Methods: Using antibiotic consumption data from the IQVIA MIDAS database, linear regression models were constructed with country-level cephalosporin, fluoroquinolone, and macrolide consumption (defined daily doses/1,000 population/year) as the outcome variables and country-specific scores of UA and POCO (obtained from the Hofstede Index), gross domestic product/capita, world region and markers of effective governance (Control of Corruption and Regulatory Quality extracted from the World Bank data) as the explanatory variables. All data, excluding the Hofstede Indices, used country-level averages for the years 2013 to 2015. Results: Complete data were available for 37 countries from 4 world regions. Consumption of cephalosporins, macrolides, and fluoroquinolones was associated with POCO and UA, but not the markers of effective governance. In the case of macrolide consumption, the association with UA narrowly missed statistical significance. Repeat analyses limited to first European countries and second to non-European countries revealed similar findings. Conclusions: More thought should be given to construct antibiotic stewardship campaigns that are tailored to the local extent of UA and POCO.