The Sterilization Operation was a United States government strategy to "sterilize" Raccoon City. The U.S. military fired lethal weaponry into the city in order to eliminate the dangerous mutagenic t-Virus. The mission was to fire a strategic missile carrying a new type of non-nuclear warhead into the heart of the city to eradicate the virus and evidence which could implicate the government.
In Resident Evil 3: Nemesis, it is shown as a single missile (armed with a top-secret new type of thermobaric non-nuclear warhead) impacted close to the Raccoon City Police Department, destroying the entire city and presumably much of the Arklay Forest.
In Resident Evil Outbreak, three missiles are seen striking the city, which causes an explosion shown as a mushroom cloud in the distance. In the game's epilogue, four missile craters can be seen: Three around the city and a large crater in the centre. This suggests that while the top-secret warhead portrayed in Resident Evil 3: Nemesis was used, another three missiles were fired, also.
In Resident Evil Outbreak File #2, the ending is portrayed differently. People evacuating by helicopter in "Up and Away" will fly past a number of missiles strike the city. Coordination is shown to be from "Heaven's Gate", a military command centre in communication with a number of fighter aircraft which are firing their missiles at the city. Again, a mushroom cloud is seen in the distance.
In Resident Evil: Degeneration, one of the news reporters at the start of the film mentions that "the missile was allegedly nuclear", adding the fact that it was assumed by the public to be nuclear due to its true nature being top-secret.
Resident Evil 6
Following the outbreak of the C-Virus in Tall Oaks, a similar operation was put into effect under order from Derek C. Simmons to eradicate evidence that could link him to the incident. Much like the portrayal in Outbreak, several missiles were used to destroy the city, its end could be seen in the forest not far from the town's outskirts.