Animal bite wounds affect more than 5 million Americans annually, resulting in 300,000 emergency department visits, 10,000 hospitalizations, and an untold number of physician office visits. Various forms of topical therapy are empirically self-employed by many patients prior to seeking medical attention. Pexiganan, a 22-amino-acid synthetic cationic analogue of the peptide magainin II, acts by selectively damaging bacterial cell membranes. We determined the MICs for pexiganan and other antimicrobial agents often used for treatment of bite wounds. Most isolates were from U.S. patients, and ∼10% were from European and Canadian patients. The comparator antimicrobials studied were penicillin, amoxicillin-clavulanate, piperacillin-tazobactam, meropenem, clindamycin, doxycycline, moxifloxacin, ceftriaxone, linezolid, and metronidazole. The MIC90s of pexiganan were 32 μg/ml (against Pasteurella multocida subsp. multocida), 16 μg/ml (P. multocida subsp. septica, Pasteurella canis, and Pasteurella dagmatis), 8 μg/ml (Pasteurella stomatis), 8 μg/ml (Eikenella corrodens), 2 μg/ml (Neisseria weaveri, Neisseria zoodegmatis, and Moraxella canis-Moraxella lacunata group), 16 μg/ml (Bergeyella zoohelcum), 64 μg/ml (Bacteroides pyogenes), 4 μg/ml (Fusobacterium russii), 32 μg/ml (Fusobacterium canifelinum), and 64 μg/ml (Prevotella heparinolytica). The concentration of pexiganan in the cream used was 8,000 μg/ml, more than 60 to 100 times the highest MIC obtained. Pexiganan exhibited a broad range of antimicrobial activity, showing potential for treating animal bite infections. A clinical trial seems warranted.