Cantharidin is a widely used treatment for molluscum contagiosum (MC) that is often favored because of its speed of application and lack of pain at the time of application. Previous studies have supported its safety and reported high parental and dermatologist satisfaction with its use. Nonetheless, a lack of safety data has contributed to ambiguous U.S. Food and Drug Administration status that has made it increasingly difficult to obtain. All children treated with cantharidin for MC at a tertiary care center between January 1, 2005, and December 31, 2011, who had at least one follow-up visit or telephone call were included in the current study. Information related to treatment with cantharidin and adverse effects was abstracted from medical records. Of 512 children identified, 405 had at least one follow-up visit or telephone call after treatment and were included in this study. Cantharidin was applied to 9,688 lesions over 1,056 visits. Fifty-seven percent of children experienced blistering, an expected effect of therapy. Eleven percent of patients experienced adverse events. The most common adverse events were pain (7%) and significant blistering (2.5%). Other side effects were rare (<1%) and included pruritus, possible mild infection, significant irritation, id reactions, and bleeding. Eighty-six percent of parents reported satisfaction with cantharidin or opted to use it again. Cantharidin is a safe treatment modality for MC and should be considered when symptomatic infection necessitates treatment. The cantharidin application protocol used in this study may serve as a model protocol with a known side-effect profile.