Background: Equine sarcoids (ES) are common, difficult to treat, and have high recurrence rates. Viscum album extracts (VAE) are used in human cancer treatment. Hypothesis: That therapy with VAE (Iscador P) is effective in the treatment of ES. Animals: Fifty-three horses (444 ES); 42 were treated with VAE or placebo as monotherapy; 11 were treated with VAE or placebo after selective excision of ES. Methods: Prospective, randomised, blinded, clinical trial. Horses were randomly assigned to treatment (VAE; n = 32) or control group (Placebo; n = 21). One milliliter of VAE (Iscador P) in increasing concentrations from 0.1 to 20 mg/mL or physiological NaCl solution was given SC 3 times a week over 105 days. Number, localization, and type of the ES were documented over 12 months. A subset of 163 clinically diagnosed equine sarcoid (CDES) lesions (95 VAE, 68 Placebo) was evaluated in detail, considering clinical findings and tumor volume. Results: No undesired adverse effects were observed except for mild edema at the injection site in 5 of 32 horses (16%). Complete or partial regression was observed in 13 horses of the VAE group (41%) and in 3 of the control horses (14%; P < .05). After VAE treatment, 48 of 95 CDES (67%) showed an improvement compared with 17 of 68 CDES in the control group (40%; P < .01). Twenty-seven CDES had disappeared completely in the VAE group (38%) compared with 9 CDES in the control group (13% NS). Conclusions and Clinical Importance: VAE (Iscador P) represents a safe and effective treatment for CDES.