The purpose of this study was to assess safety and efficacy of high dose Yunnan Baiyao (YB) administered preoperatively for dogs undergoing spay or neuter procedures. A total of 42 dogs recruited from a local shelter and nominal fee spay/neuter clinic completed the study. Dogs were randomly assigned to Treatment Group (n = 20) and Control Group (n = 22). The Treatment Group received a single dose (100 mg/kg) of YB, between 2 to 4 hours prior to surgery, whereas the Control Group received no treatment. Blood loss during surgery, based on weight gain of gauze squares, was collected as the outcome measurement along with monitoring for adverse effects. To account for blood loss in proportion to body weight, the body weight normalized blood loss (WNBL) was calculated (g/kg). Both surgeon and person weighing gauze squares were blinded as to which subjects received YB treatment. Compared to the Control Group (median = 0.067), the WNBL median for Treatment Group (median = 0.044) was reduced by 33% (neuter + spay combined). Several dogs (1 control, 2 treatment) that underwent the spay procedure had markedly increased blood loss (3x-5x) related to reproductive cycle stage, poor health/breed predisposition and were designated outliers. Statistical evaluation (outliers removed) demonstrated a statistically significant, 4-fold decreased blood loss in the YB treated dogs undergoing the spay procedure (p=0.026). In addition, no adverse effects were observed related to treatment. This study indicates that Yunnan Baiyao can be useful in decreasing intraoperative blood loss in dogs undergoing the spay procedure.