A Canadair CRJ-200LR, N77181, operated by Mesa Airlines as flight 7264, was substantially damaged when the thrust reverser translating cowling separated from the left engine during cruise flight and struck the horizontal and vertical stabilizers. The airplane was near the eastern shore of Lake Michigan, about 35 miles west-northwest of Grand Rapids, Michigan, when the accident occurred. The flight crew received a left thrust reverser unlock indication while holding for takeoff. The captain cycled the reverser, and had decided to return to the gate when the messages cleared. With the issue apparently resolved, he elected to takeoff. The captain reported experiencing a small vibration on climb out and, a short time later, he heard a “loud bang” and the “aircraft pitched and yawed/rolled to [the] left.” The autopilot disengaged and the left thrust lever moved to idle during the event. The first officer ran the checklist to stow the reverser. The captain decided to continue to the intended destination because the thrust reverser messages had cleared and the vibrations had stopped. The flight subsequently landed uneventfully. The flight data recorder (FDR) indicated that the left engine vibration levels were elevated during the accident flight. Approximately 3 minutes into the flight, the left engine thrust reverser unlocked parameter changed to “On” for about 1 second. About 11 minutes and 20 seconds after takeoff, the left engine vibration level increased momentarily, and both the left and right engine speeds and fuel flows began to decrease. As the decrease in fuel flows was occurring, the airplane rolled right, left, and right again over about a 4-second period. The decrease in engine parameters lasted over 3 minutes before returning to normal. The left engine thrust reverser unlock parameter indicated “On” for about 4 seconds during that time. The left engine vibration levels decreased after the event, below the levels previously recorded during the flight, and approximately to the level of the right engine vibration. The vibration and engine speed variations suggested separation of the left engine translating cowling at that point. The left engine thrust reverser deploy parameter remained in the “Off” state for the entire flight. Additionally, the FDR data revealed that the left engine vibration levels were elevated and left engine thrust reverser did not deploy on the two previous flights. The post accident inspection revealed that the left engine translating cowl had separated from the engine assembly and damaged the empennage. Damage to the thrust reverser components was consistent with prior operation with the reverser out of alignment and jamming of the translating structure. In-flight separation of the left engine thrust reverser translating cowling due to intermittent binding and jamming of the reverser on the accident flight and on previous flights. Contributing factors were the inadequate maintenance action by the operator due to their failure to properly resolve the prior reverser malfunctions, the failure of the pilots of previous flights in not referring earlier reverser deployment failures for maintenance action, and incomplete company/manufacturer’s procedures because they did not address anomalous reverser indications during ground operations.