This study assesses the efficiency of higher education institutions (HEIs), considering the social, environmental and cultural factors (pro-sustainability), and at the same time examines how this efficiency can influence regional quality of life (QoL). The study adopts a two-step methodology. In the first step, the standard Data Envelopment Analysis (DEA) is used to estimate the efficiency scores of 23 Portuguese public HEIs; and in the second step, a multivariate logit regression is performed to assess the role played by the HEIs’ pro-sustainability efficiency in regional QoL. The main findings reveal that the HEIs located in the Greater Lisbon area have a higher pro-sustainability efficiency, but that efficiency is more significant regarding social factors. Concerning the contribution of pro-sustainability efficiency to the region’s QoL, this is significant for all the components, with the environmental and cultural aspects contributing positively to this significance.