It's a practical question of what paper you have available. The US standard paper size is 8 1/2" x 11" (or 216 mm x 279 mm). The A4 standard is 210 x 297. So the American paper is wider and shorter, though not by much -- 1/4" wider and 5/8" shorter.
The Canadian and British scripts usually have internal margin adjustments to maintain the proper proportion. The font needs to be 12 pt Courier. NO EXCEPTION. If you are submitting electronically as a PDF, it doesn't matter. In that case, go with the US Standard. If you are printing it out, it is unlikely to make as significant a difference as poor formatting and other writing issues. Readers vary but paper size is usually the last worry--unless you send it on heavy-weight, scented, colored paper with illustrations. A neatly printed script, well-formatted with a great first ten pages is more important.
If you have access to US standard, I would probably use that for my submission. If you do not have ready access, it's the content and organization that will be most important.
The A4 has slightly more surface area, so it becomes heavier and more expensive to ship for larger scripts. Anyone to whom you ship it for review may refuse to send it back since it's from overseas. If you are querying blind, you may wish to see if they will accept a PDF submission. If you've been asked to submit a script, I would focus on the content and organization.
Good luck
