In prokaryotes, translation initiation typically depends on complementary binding between the Shine-Dalgarno (SD) motif in the 5’ untranslated region of mRNAs and the 3' tail of the 16S ribosomal RNA. In coding regions, “internal” SD-like motifs can cause ribosomal pauses and are proposed to face strong negative selection. However, these motifs may also evolve under neutral or positive selection in species that do not use SD-based translation initiation; in AT-rich genomes where the G-rich SD motif is rare; and when translational pauses are beneficial for protein folding or targeting. To determine the nature and consequences of selection acting on internal SD-like motifs, we analysed their frequency in 284 prokaryotes. After accounting for genome GC content, we found that internal SD-like motifs are relatively rare in 227 species, but also in three of seven species that do not use the SD mechanism. The depletion was stronger in GC-rich genomes, mesophiles, and in N-terminal gene regions. In contrast, 50 species either showed no signature of avoidance or were enriched in internal SD-like motifs. Further, C-terminal regions of genes in operons or those closely followed by a downstream gene were relatively enriched in such motifs. Finally, we found no empirical correlation between the predicted and observed fitness impact of altering internal SD-like motifs in a bacterium. Together, our results show that selection against internal SD-like motifs is neither consistently strong nor predictable across genes and species. The evolution of internal SD-like motifs is governed by multiple factors including GC content and genome organization, and other motifs in prokaryotic genomes may evolve under similarly complicated evolutionary pressures.