Before being taken to the ingenio (amalgamation refinery), excess material would be broken off of the silver ore. At the refiner, it was ground to a fine sand (harina) by an arrastra or stamp mill, which consisted of a rotating shaft fitted with heavy iron stamps that crushed the ore against a mortar block. The harina was then placed in heaps of 2,000 lbs or more, to which was added salt, water, magistral (essentially an impure form of copper sulfate, CuSO), and mercury. This was then mixed by bare-legged Indian laborers or by horses or mules and spread in a 1-to-2-foot-thick (0.30 to 0.61 m) layer in a patio (a shallow-walled, open enclosure). After six to eight weeks of mixing and soaking in the sun, a complex reaction converted the silver to native metal, which formed an amalgam with the mercury. The mixture was then washed and strained through a canvas bag before being placed into a hooded oven. Heating this amalgam vaporized the mercury, leaving the silver. The mercury vapor would then condense on the cooled hood, where it could be collected and reused. The amount of salt and copper sulfate varied from one-quarter to ten pounds of one or the other, or both, per ton of ore treated. The decision of how much of each ingredient to add, how much mixing was needed, and when to halt the process depended on the skill of an  (English: quicksilver man). The loss of mercury in amalgamation processes is generally one to two times the weight of silver recovered.
The patio process was the first form of amalgamation. However, it is unclear whether this process or a similar process—in which amalgamation occurred in heated vats rather than open patios—was the predominant form of amalgamation in New Spain, as the earliest known illustration of the patio process dates from 1761. There is substantial evidence that both processes were used from an early date in New Spain, while open patios were never adopted in Peru. Instead, Andean refiners placed milled ore in stone tanks vaulted over a fire, which helped accelerate amalgamation by mitigating the bitterly cold temperatures at the high elevation of the Andean mines. Both processes required that ore be crushed and refiners quickly established mills to process ore once amalgamation was introduced. Water mills were common in the Andes, powered by man-made dams, while in New Spain, where water was relatively scarce, mills were often powered by horses or other draft animals.
Due to amalgamation's reliance upon mercury, an expansion of mercury production was central to the expansion of silver production. A key source of mercury was at Huancavelica, Peru, where vast deposits were discovered in 1563. Additional mercury was sourced from Almadén, Spain, and Idrija in present-day Slovenia. From shortly after the invention of mercury amalgamation to the end of the colonial period, the Spanish crown maintained a monopoly on mercury production and distribution, ensuring a steady supply of royal income. Fluctuations in mercury prices generally resulted in corresponding increases and decreases in silver production. Crown control over these prices could be used to intentionally depress or stimulate silver production in Spanish colonies.