Quarantine is designed primarily to prevent the introduction of transmissible diseases to zoological collections. Improvements in preventive medicine, disease eradication, and comprehensive pathology programs call into question current industry quarantine standards. Disease risk analysis was used at the San Diego Zoo (SDZ) and the SDZ Safari Park to eliminate quarantine isolation and transmissible disease testing for animals transferred between the two institutions. To determine if a risk-based approach might be valid between other institutions and SDZ, we reviewed quarantine data for animals arriving at SDZ from 81 Association of Zoos and Aquariums (AZA)–accredited and 124 other sources (e.g., non–AZA-accredited institutions, private breeders, private dealers, governmental bodies) over a 5-yr period (2009–2013). No mammal or herptile failed quarantine due to transmissible diseases of concern. Approximately 2.5% of incoming birds failed quarantine due to transmissible disease; however, all 14 failed individuals were obtained from three nonaccredited sources (private breeders, confiscation). The results of our study suggest that a risk-based approach could be used to minimize or eliminate quarantine for the transfer of animals from institutions with comprehensive disease surveillance programs and/or preshipment testing practices. Quarantine isolation with testing remains an essential defense against introducing transmissible diseases of concern when there is a lack of health knowledge about the animals being received.