Sexual dysfunction is a common toxicity and detrimental for the quality of life of women treated with chemoradiotherapy for anal cancer. Sexual dysfunction occurs because the vagina is closely approximated to the anal canal and typically receives substantial doses of radiation. Strategies for mitigation have largely been focused on posttreatment therapy and symptom management. The use of daily vaginal dilator placement during radiotherapy to mitigate dose to the vagina has been previously explored with modest gains, while proton therapy is under active investigation for the treatment of anal cancer. Use of proton therapy for anal cancer reduces dose to some organs at risk but may inadvertently increase vaginal toxicity if the proton beam terminates in the vaginal tissue. Herein, we present the case histories of 2 women treated for squamous cell carcinoma of the anal canal with the novel combination of intensity-modulated proton therapy and daily vaginal dilator placement to maximally reduce dose to the vagina and protect it from areas of increased energy deposition at the end of the proton range.