In bacteria, translation re-initiation is crucial for synthesizing proteins encoded by genes that are organized into operons. The mechanisms regulating translation re-initiation remain, however, poorly understood. We now describe the ribosome termination structure (RTS), a conserved and stable mRNA secondary structure precisely localized downstream of stop codons, which serves as the main factor governing re-initiation efficiency in a synthetic Escherichia coli operon. We further report that in 95% of 128 analyzed bacterial genomes representing all phyla, this structure is selectively depleted when re-initiation is advantageous yet selectively enriched so as to insulate translation when re-initiation is deleterious.