Howard Bashman of How Appealing asks:

By the way, am I the only one who prefers “an URL” to “a URL” (Dixie Chicks excluded)?

The short answer: probably not.

My general rule: use an when the vowel sound is pronounced at the beginning of the subsequent word, and a otherwise. In the case of “H”: an hour, but a hat. “Y” is also potentially problematic, although usually in English it is not pronounced as “i” at the beginning of a word—but one might refer to, or call one’s self, “an Yglesias fan.”

But letters at the beginning of abbreviations could be a bigger issue: “A”, “E”, “I”, and “O” have clear vowel sounds at the beginning, while “U” is pronounced like yew, with the “yuh” sound for y. So “a URL” seems more appropriate to me, if you speak it as a collection of letters—e.g. U-R-L. However, if you pronounce it like the name or title “Earl,” an would work better, and there seems to be a good number of people (techies and non-techies) out there who do.

Incidentally, common British practice would uppercase an abbreviation to be spoken as initials—e.g. USA—and capitalize an abbreviation prounounced like a word—e.g. Nato—but that’s not used west of the pond, so there’s no obvious guide except knowledge of the language. Some also argue that the latter type of abbreviation is the only type that can be called an “acronym,” a position I am agnostic on.