Can I use a different stone for each side in a three-stone ring?

Yes. I've set a ruby on one side and a sapphire on the other, and it worked because the client cared about the colors more than the symmetry.

Most three-stone rings I make use matched sides. A center stone and two identical sides create a rhythm that reads deliberate, not accidental. Put a different stone on each side and you're asking the eye to accept two separate side accents instead of one quiet bookend. Some people love that. Some people regret it by year three.

If you go mismatched, pick the center first and let it dominate. Side stones should be smaller, lower set, and quieter in color. A 0.60 carat pear sapphire and a 0.55 carat pear tsavorite flanking a 1.5 carat diamond can work beautifully. Two bright stones arguing with a small center will not.

Durability matters more than it does in a solitaire. Side stones catch doorknobs and counter edges. Pairing a sapphire (Mohs 9) with an emerald (Mohs 7.5 to 8) means one side will chip sooner than the other. I'll still set that combination, but I'll tell you to expect more maintenance on the emerald. For daily wear, I'd push you toward sapphires, spinels, chrysoberyl, or tsavorite on both sides, just in different colors or cuts.

A matched pair of side stones is often cheaper per carat than two different stones cut to the same proportions, because you're not paying a cutter to force a match and you're not paying me to build two separate seats that may never look identical in the metal. Last fall I built a ring for a client named Priya who wanted an oval diamond center with one pink sapphire side and one padparadscha side. The colors were lovely but the stones' depths differed enough that I had to rebuild two baskets, which added about 18% to the setting cost and a week of back-and-forth while the client approved the new wax. She loved it. She also said she wouldn't do it again.

If you bring me two inherited stones and want them as sides, I'll usually say yes if the cuts are close in outline and the colors don't fight. If one is a cabochon and the other is a faceted emerald-cut, no. That ring will look like a ransom note.

Allowed, doable, sometimes wonderful. Make the center dominate, match the side stone outlines as closely as you can, and be honest about daily wear.