Antivenom is currently the cornerstone of treatment for snake envenomation in the United States (US). However, its use in clinical practice by physicians varies and is not universal. Our study objective is to explore physicians’ perceptions of antivenom use and experience with snake envenomation treatment, to identify factors that influence treatment decisions and willingness to administer. We performed a qualitative study based on a grounded theory framework including in-depth interviews via online video conferencing with physicians practicing in emergency departments (ED) across the US. Participants were selected based on purposive sampling methods and data analysis followed by a combination of inductive and deductive strategies, conducted by two researchers. The codebook was created based on the interview guide and the first four interviews. Subsequent transcripts were independently coded by two researchers and a content memo was created. The two researchers then discussed their analysis of each interview and synthesized the findings into an analytical memo of all emergent themes. The codebook and findings were continuously discussed with the other investigators. Sixteen in-depth interviews with physicians from nine states across the US were conducted. The participants’ specialties include Emergency Medicine (EM), pediatric EM, and Medical Toxicology. The experience of treating snake envenomation ranged from only didactical knowledge to having treated over one hundred cases. Emergent themes were as follows: treatment approach and factors influencing clinical decision making, antivenom prescription and perceived competence as well as treatment hesitancy, commonly used resources to inform clinical practice, and the role of scientific evidence and suggestions to improve management. Overall, cost-related concerns were major barriers to administer antivenom. This was especially the case when the indications and effectiveness were not perceived to outweigh the potential financial burden on the patient. The potential to decrease recovery time and long-term morbidity was not commonly reported by participants as an indication to treat with antivenom. Common suggestions to address the lack of available follow-up from the ED was a system to receive information on long-term recovery through individual case follow up information and/or increased scientific evidence of long-term outcomes. Envenomation severity and perceived physician competence based on prior education and clinical experience also impacted the decision to treat. Physicians were not concerned about the safety of antivenom and most felt that potential side effects were mild and manageable. Resources such as Poison Control were well received and commonly used to guide the treatment plan. The need for clinical guidelines and updated treatment algorithms with clinical measurable indicators was a stated need to help the decision-making process, especially amongst those with low exposure to snake envenomation. A major barrier to physician use of antivenom is concern about cost for the patients. Additionally, inconsistent awareness of potential benefits during recovery further increase inconsistent antivenom treatment practices. Antivenom safety concerns were not a major barrier.