To assess the effect of hyperbaric oxygen therapy (HBOT) on Crotalinae envenomation-induced wound swelling and severity and pain in dogs, and to describe the safety and complications of HBOT. Prospective, randomized, controlled, blinded study (2017-2021). University teaching hospital, private veterinary practice. Thirty-six client-owned dogs presenting within 24hours of a confirmed or suspected naturally occurring Crotalinae snake bite injury were enrolled between 2017 and 2021. In addition to the standard of care treatment, dogs received 2 interventions with either HBOT (n=19) or control (n=16) within 24hours of hospital admission. Dogs receiving HBOT were pressurized over 15 minutes (1psi/min), maintained at a target pressure of 2 atmosphere absolute (ATA) for 30 minutes, and decompressed over 15 minutes. Control dogs received 1 ATA for 1hour. Local wound swelling, wound severity score, and pain score were assessed at admission, before and after each intervention, and at hospital discharge. There was no significant difference in wound swelling (P=0.414), severity score (P=1.000), or pain score (P=0.689) between HBOT and control groups. Pain decreased significantly over time regardless of the study intervention (P<0.001). There were no major adverse effects associated with either study intervention. HBOT did not significantly alter the short-term recovery from Crotalinae envenomation in this study population. However, the study might be underpowered to detect a significant treatment effect.