The average Thanksgiving turkey weighs 15 pounds, so your 21.5-pound turkey is a hefty bird and thus requires a relatively long roasting time -- about 4.5 to 5 hours at 325 degrees. The extended cooking time presents you with two main challenges: preventing the meat from drying out and keeping the skin from overcooking before the meat is done. The keys are to prep your turkey properly, cover it for the first part of the cooking process, refrain from basting and avoid opening the oven frequently.
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SET UP THE OVEN: Position an oven rack low enough that the middle of the turkey will be centered in the oven chamber. Preheat the oven to 325 degrees Fahrenheit.
PREPARE THE TURKEY: Remove the turkey neck and giblets from the body cavity of the turkey if necessary. Though conventional wisdom says to rinse the bird before cooking, it's not necessary and can be a food safety issue. Rinsing a huge, slippery turkey in your kitchen sink is awkward and can splash harmful bacteria all over the sink and counter -- and you. So skip the bird bath, and rely on cooking the turkey to the proper internal temperature to kill any bacteria.
Wash anything that comes in contact with the raw turkey -- utensils, dishes, the countertop and your hands -- in hot, soapy water to prevent spreading bacteria to other dishes you might be cooking. If the raw turkey touches your apron or clothing while you're handling it, change clothes before you continue working in the kitchen.
POSITION THE BIRD: Insert a cooking rack into a shallow roasting pan. Place the turkey on the rack, breast side up. Tuck the ends of the legs under the loose skin at the tail area, or tie the ankles together with kitchen twine. Tuck the ends of the wings under the shoulders.
KEEP THE SKIN MOIST: Brush the surface of the turkey with melted butter or olive oil. Sprinkle salt and ground black pepper over the bird. Add any other seasonings according to taste or your recipe.
TO STUFF OR NOT TO STUFF: An unstuffed turkey takes a little less time to cook, which is an advantage with a 21.5-pound bird. And although many people like to cook the stuffing inside the turkey, the USDA recommends baking it in a separate casserole dish for safer, more even cooking. However, if you choose to stuff the bird, combine the wet and dry ingredients at the last minute. Pack the turkey loosely with the stuffing, and put it in the oven immediately. Alternatively, you can let the turkey bake for half the recommended time, and then stuff it and return it to the oven. This method allows you to prep the stuffing while the turkey starts to cook.
FINISH THE PREP: Pour a cup of chicken broth or water into the bottom of the roasting pan. Stick an oven-safe meat thermometer into the deepest area of one thigh muscle. Make sure the thermometer is not in contact with bone, and that its tip is in the middle of the muscle. Either place the roasting pan lid on the turkey or tent the bird with a large sheet of aluminum foil. Put the turkey in the oven.
COOK THE TURKEY: Rotate the roasting pan once an hour to promote more even cooking for a turkey this large. Turning the pan helps account for temperature variances throughout the oven, explains the Science of Cooking website. If possible, keep the roasting pan from touching the edges of the oven to prevent obstructing the heat flow. After 60 to 90 minutes, remove the aluminum foil.
CHECK ON THE BIRD: Replenish the chicken broth or water in the bottom of the pan as it evaporates. If you want moist, tender skin, refrain from basting the turkey, advises the University of Illinois. Basting doesn't make the turkey meat more moist; it only promotes browning of the skin. Opening the oven for frequent basting also lets heat out, extending what is already a long cooking time. If you have an oven light, use that to check in on the cooking process, rather than opening the door.
OBSERVE COOKING TIME: Roast the turkey until the meat thermometer indicates the internal temperature in the thigh muscle is at least 165 degrees Fahrenheit. If you stuffed the turkey, use the meat thermometer to make sure the center of the stuffing is also at least 165 degrees Fahrenheit. Expect it to take 4.5 to 5 hours to cook a 21.5-pound turkey at 325 degrees Fahrenheit -- if your turkey is unstuffed. If it's full of your favorite stuffing, add at least 15 minutes to the total cooking time. Determine when the turkey is done by internal temperature only. Don't rely on the fact that your turkey's pop-up thermometer has sprung, as cooking time always varies.
GET READY TO EAT: Remove the turkey from the oven and place it on a serving platter or large cutting board. Let the large bird rest 20 to 30 minutes before carving to make it easier to slice and serve. Then, if you stuffed your turkey, remove the stuffing before carving.