Antibiotic resistance is a global public health threat exacerbated by medically unwarranted or improper antibiotic use. Pharmacy counters at the U.S.–Mexico border provide an example of where lay decisions to use antibiotics in ways considered “risky” may be initiated and negotiated. We test how cultural and public health knowledge of antibiotics is distributed among pharmacy staff, local Mexican clients, and U.S. medical tourists in the bordertown of Nogales using a cultural consensus tool. We find that shared cultural models across these groups include public health statements; however, other shared statements are likely to reinforce antibiotic sales at pharmacy counters by those on both sides of the purchase as economic, rather than therapeutic, encounters. From a public health perspective, border pharmacy counters are not a location where increased “safe” knowledge about antibiotic use is being transmitted. However, we do find a positive relationship between “safe” knowledge and reductions in risky behavior.