Polyploidy, the doubling of genomic content, is a widespread feature, especially among plants, yet its macro-evolutionary impacts are contentious. Traditionally, polyploidy has been considered an evolutionary dead-end, whereas recent genomic studies suggest that polyploidy has been a key driver of macro-evolutionary success. Here we examine the consequences of polyploidy on the time scale of genera across a diverse set of vascular plants, encompassing hundreds of inferred polyploidization events. Likelihood-based analyses indicate that polyploids generally exhibit lower speciation rates and higher extinction rates than diploids, providing the first quantitative corroboration of the dead-end hypothesis. The increased speciation rates of diploids can, in part, be ascribed to their capacity to speciate via polyploidy. Only particularly “fit” lineages of polyploids may persist to enjoy longer term evolutionary success.