Example methods are provided to build a smart file reputation cache at a cloud, and to provide the smart file reputation cache to an antivirus (AV) endpoint such as a virtualized computing instance in a virtualized computing environment. Training techniques can be used to build the smart file reputation cache at the cloud, based on information learned from existing AV endpoints and a management server. The smart file reputation can then be provided to newly installed AV endpoints for local access, instead of the AV endpoints sending file reputation requests to the cloud.