Background In endemic communities, zoonotic tungiasis, a severe skin disease caused by penetrating female sand fleas, is a public health hazard causing significant human and animal morbidity. No validated drugs are currently available for treatment of animal tungiasis. Due to the reservoir in domestic animals, integrated management of human and animal tungiasis is required to avert its negative effects. Methods and principal findings A topical aerosol containing chlorfenvinphos 4.8%, dichlorphos 0.75% and gentian violet 0.145% licensed to treat tick infestations, myiasis and wound sepsis in animals in the study area, was tested for its potential tungicidal effects in a randomized controlled field trial against pig tungiasis in rural Uganda. Animals with at least one embedded flea were randomized in a treatment (n = 29) and a control (n = 26) group. One week after treatment, 58.6% of the treated pigs did not show any viable flea lesion whereas all control pigs had at least one viable lesion. After treatment the number of viable lesions (treated median = 0, overall range = 0–18 vs. control median = 11.5, range = 1–180) and the severity score for estimating acute pathology in pig tungiasis (treated median = 1, range = 0–3.5 vs. control median = 7, range = 0–25) were significantly lower in treated than in control pigs (p < 0.001). In the treatment group the median number of viable flea lesions decreased from 8.5 to 0 (p < 0.001). Similarly, the median acute severity score dropped from 6 to 1 (p < 0.001). Every pig in the treatment group showed a decrease in the number of viable fleas and tungiasis-associated acute morbidity while medians for both increased in the control group. Conclusions The study demonstrates that a topical treatment based on chlorfenvinphos, dichlorphos and gentian violet is highly effective against pig tungiasis. Due to its simplicity, the new approach can be used for the treatment of individual animals as well as in mass campaigns. Author Summary Infection with the sand flea Tunga penetrans causes severe disease in humans and animals. There are no validated drugs for treatment of animal tungiasis preventing implementation of integrated tungiasis control interventions targeting human and animal infections. A field trial was conducted to evaluate the effects of a commercial insecticidal aerosol containing chlorfenvinphos 4.8%, dichlorphos 0.75%, and gentian violet 0.145%, which is licensed to treat tick infestations, myiasis and wound sepsis, on tungiasis in pigs, the major animal reservoir in rural hyperendemic villages in Uganda. Infected pigs were recruited and randomly assigned to treatment (n = 29) and control (n = 26) groups. Seven days after a single application of the aerosol onto the affected body parts, almost 60% of the treated pigs were cured while all control pigs had at least one penetrated sand flea. The number of viable sand fleas and the severity of the tungiasis were significantly lower in the treated pigs than in the controls. This demonstrates for the first time that a simple and effective topical treatment for animal tungiasis based on two organophosphate insecticides and an antibacterial agent can be used to cure individual animals and can be integrated in tungiasis control campaigns.