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I carry four different guns in three different configurations. Two are .45 caliber 1911s, which are carried cocked and locked. One is a .40 USP Compact, which I can carry either cocked and locked, or decocked, as is my fancy. When I carry decocked, I generally leave the safety off. The last is a small S&W revolver in .38 Special.

It has become my habit to sweep my thumb down, whether or not there is a safety in play, for either the 1911s or the USP. The revolver is so radically different in feel in my hand from the other three that I seriously doubt I would ever be confused about how to use it.

Finally, I practice with all three calibers, so there is no familiarity issue.