Using an online public engagement experiment, we probed the views of 617 participants on the use of pigs as research animals (to reduce agricultural pollution or to improve organ transplant success in humans) with and without genetic modification and using different numbers of pigs. In both scenarios and across demographics, level of opposition increased when the research required the use of GM corn or GM pigs. Animal numbers had little effect. A total of 1037 comments were analyzed to understand decisions. Participants were most concerned about the impact of the research on animal welfare. Genetic modification was viewed as an intervention in nature and there was worry about unpredictable consequences. Both opponents and supporters sought assurances that concerns were addressed. Governing bodies for animal research should make efforts to document and mitigate consequences of GM and other procedures, and increase efforts to maintain a dialogue with the public around acceptability of these procedures.