Aim: This study aimed to evaluate the benefits of Arnica montana on post-operative blood loss and seroma production in women undergoing unilateral total mastectomy by administering Arnica Montana 1000 Korsakovian dilution (1000 K). Materials and Methods: From 2012 to 2014, 53 women were randomly assigned to A. montana or placebo and were followed up for 5 days. The main end point was the reduction in blood and serum volumes collected in drainages. Secondary end points were duration of drainage, a self-evaluation of pain, and the presence of bruising or hematomas. Results: The per-protocol analysis revealed a lower mean volume of blood and serum collected in drainages with A. montana (−94.40 ml; 95% confidence interval [CI]: 22.48-211.28; P = 0.11). A regression model including treatment, volume collected in the drainage on the day of surgery, and patient weight showed a statistically significant difference in favor of A. montana (−106.28 ml; 95% CI: 9.45-203.11; P = 0.03). Volumes collected on the day of surgery and the following days were significantly lower with A. montana at days 2 (P = 0.033) and 3 (P = 0.0223). Secondary end points have not revealed significant differences. Conclusions: A. montana 1000 K could reduce post-operative blood and seroma collection in women undergoing unilateral total mastectomy. Larger studies are needed with different dilutions of A. montana to further validate these data.