If we were to keep macrolide consumption below a certain threshold, would this reduce the probability of macrolide resistance emerging? No study that we are aware of has addressed this question. We, therefore, assessed at a country level if there was a macrolide consumption threshold for the selection of a prevalence of macrolide resistance of over 5% in Streptococcus pneumoniae, Treponema pallidum, and Mycoplasma genitalium. In this ecological-level analysis, we found evidence for a macrolide consumption threshold of 1.3 defined daily doses per 1,000 inhabitants per day (DID) for M. genitalium, 1.8 DID for T. pallidum, and 2.3 DID for S. pneumoniae. Our results provide further motivation for macrolide stewardship campaigns that strive to reduce macrolide consumption to levels below at least 2 DID.