In this article, we contribute to the scant literature covering quantitative studies on the determinants of the non-academic staff incidence in higher education institutions by analysing how the proportion of non-academic staff is related to key features such as size, prestige, year of foundation and financial structure of universities. We apply nonlinear regression analysis to compare HEIs across Europe and the USA, taking into account time and cross-country heterogeneity of the two balanced panel datasets concerning European and American universities over a period of 6 years (2011–2016 for Europe and 2012–2017 for the USA). Evidence suggests that in both Europe and the USA, public and larger (if sufficiently large) as well as more research-oriented units are characterised by a higher proportion of non-academic staff. In Europe, we observe an inverted U-shaped effect of the share of non-personnel expenditure and the foundation year on the proportion of non-academic staff, while the proportion of non-academic staff decreases with the share of core and third-party funding. For the USA, we obtain similar findings except that the share of core funding and third-party funding is characterised by a U-shaped effect, and the impact of the share of non-personnel expenditure has no empirical effect on the proportion of non-academic staff. Additionally, we discover that some factors that contribute to the proportion of non-academic staff may constitute indicators of performance, suggesting the need for further research to extend our knowledge on the complex issue of the role played by non-academic staff in university performance.