There are 7000-8000 venomous snake bites annually in the USA. Antibiotics are commonly administered to bite victims because infection is difficult to differentiate from local tissue injury following envenomation. The Arizona Poison and Drug Information Center (APDIC) in Tucson oversees antivenom administration for 14 Arizona counties. Records (1999-2021) were searched for antibiotic use and confirmed infections after a rattlesnake bite. There were 4160 calls to APDIC regarding rattlesnakes. After excluding bites to animals, 'dry bites', prisoners and records with missing data, 2059 records were evaluated. Systemic antibiotics were administered to 206 patients (10% of bite victims). Twenty patients (0.97%) had confirmed infections, including cellulitis (n=10), fasciitis (n=4), abscess (n=3) and osteomyelitis (n=3). Five of the victims had positive blood cultures. The presence of tissue necrosis, leukocytosis, fever and elevated fibrinogen levels did not discriminate between toxic effects of venom and infection. Confirmed infections following a rattlesnake bite are uncommon (0.97% of bites). Physicians should refrain from prescribing antibiotics, as they are not justified for most rattlesnake bite victims and the variety of pathogens encountered precludes use of any single effective antibiotic.