The company that makes this product incorporated in 1926 as American Home Products (AHP) and "one of AHP's earliest prizes was the acquisition of a sunburn oil in 1935 that the company transformed into Preparation H, which became one of the world's best-selling hemorrhoid treatments.

The active ingredients range from simple caffeine moisturizers with witch-hazel astringent to preparations containing drugs such as phenylephrine, pramoxine, and hydrocortisone.

Some Preparation H products have phenylephrine, a drug that constricts blood vessels, in a 0.25% concentration, as well as shark liver oil.

The Canadian formulation has acquired a market in the United States as a skin cream with an anti-wrinkle active ingredient.

[citation needed] In Greece, the active ingredients of Preparation H are 1% w/w yeast extract and 3% w/w shark liver oil.