The picornaviruses’ genome consists of a positive-sense ssRNA. Like many picornaviruses, cardioviruses synthesize two distinct polyprotein precursors from adjacent but non-overlapping genome segments. Both the [L-1ABCD-2A] and the [2BC-3ABCD] polyproteins are proteolytically processed to yield mature capsid and non-structural proteins, respectively. An unusual translational event, known as ‘StopGo’ or ‘Stop-Carry on’, is responsible for the release of the [L-1ABCD-2A] polyprotein from the ribosome and synthesis of the N-terminal amino acid of the [2BC-3ABCD] polyprotein. A common feature of these viruses is the presence of a highly conserved signature sequence for StopGo: –D(V/I)ExNPG↓P–, where –D(V/I)ExNPG are the last 7 aa of 2A, and the last P- is the first amino acid of 2B. Here, we report that, in contrast to encephalomyocarditis virus and foot-and-mouth disease virus, a functional StopGo does not appear to be essential for Theiler’s murine encephalomyelitis virus viability when tested in vitro and in vivo.