We describe the clinical results of psoriatic skin lesions in 12 adult patients with long-standing mild to moderate plaque psoriasis resistant to treatment with various topical and systemic therapies that were treated with a bovine-based collagen ointment (20% collagen powder of bovine origin in a petrolatum base) for 4 to 6 weeks. The product was applied once every evening, with enough to cover the lesion, and spread by gentle massage until the ointment was fully absorbed. One localized plaque per participant was selected for treatment. Response to treatment was assessed by changes in the signs and symptoms of plaque psoriasis in the target lesions (ie, erythema, desquamation, hyperkeratosis, itching, fissures/cracks) rated on a scale from 0 (not present) to 4 (severe/intense) as well as physician global assessment (PGA) with scores from 1 (unchanged/worse) to 6 (cleared [100% improvement]). The treatment group included 4 men and 8 women with a mean age (standard deviation [SD]) of 45.9 (12.6) years (range, 26–61 years). Psoriasis had been present for a mean (SD) of 20.7 (9.4) years. The mean duration of treatment was 40 days (range, 30–45 days). The median interquartile range PGA score of 1.50 (range, 0–2.75) at baseline increased to 4.5 (range, 4–5) at the end of treatment (P=.002). There was a statistically significant improvement of erythema (63.9%), desquamation (63.9%), hyperkeratosis (77.8%), itching (82.6%), and fissures/cracks (91.2%) at the end of the study compared to baseline values (all P<.05). The cosmetic characteristics (eg, appearance, texture, aroma, softness, odor, consistency, ease of application) of the product were well-accepted. No side effects or adverse reactions were observed. The confirmation of these findings in a larger number of patients, particularly in controlled prospective studies, could represent an important advance in the therapeutic armamentarium for patients with plaque psoriasis given the excellent safety profile of this nonsteroidal collagen-based ointment.