Following the success of the first title in Japan, Capcom quickly announced Resident Evil Outbreak File #2 for a release in fall 2004. File #2 is more of an extension of the first game than a whole new game itself. The same eight characters from the first title return with similar abilities, and the game takes place once again in a zombie-run Raccoon City.

Five new scenarios are available, and the first four are available from the beginning. One scenario takes place in a zoo, another in a subway, and one in a forest-like setting. The fourth scenario is a modified version of the Raccoon Police Department, which first appeared in Resident Evil 2 and Resident Evil 3: Nemesis. The fifth is an Umbrella laboratory. In Japan, the game came packaged with a demo of Devil May Cry 3 (if pre-ordered). Despite the financial success of the first title, File #2 sold roughly 40% of what the first did when it was released in Japan, dampening the chances of a future installment. As of March 31, 2007 Capcom has shutdown all servers for the online mode.