When should an aircraft set the altimeter to a standard pressure during level cruise?

An aircraft should set the altimeter to a standard pressure when it is no longer in an area where local altimeter settings are provided, specifically after leaving the altimeter setting region. This transition typically happens when the aircraft climbs through a certain altitude, often around 18,000 feet in the United States, where the altimeter setting changes to the standard pressure of 29.92 inches of mercury (Hg).

Setting the altimeter to a standard pressure is important for maintaining uniform altitude separation between aircraft. When all aircraft at higher altitudes reference the same pressure setting, it ensures that altitude readings are standardized, reducing the risk of miscalculations or altitude encroachments in the busy airspace.

In contrast, areas where local altimeter settings are provided require pilots to adjust their altimeters based on local atmospheric conditions, which are critical for safe operation at lower altitudes. Therefore, it wouldn't be appropriate to set the altimeter to a standard pressure before takeoff or upon entering the altimeter setting region, as accurate local pressure is essential for safe maneuvering prior to reaching cruising altitude.