Solid organ transplantation is the preferred method of treatment for a number of advanced medical conditions, but it requires systemic immunosuppression to prevent transplant rejection. The authors report 2 unique cases of persistent eyelid edema following solid organ transplantation believed to be related to their systemic immunosuppression. The eyelid findings developed after initiation of the immunosuppressant sirolimus. In 1 patient, the eyelid edema has persisted despite discontinuation of the medication. In the second patient, the immunosuppression could not be altered; therefore, he underwent surgical excision of the edematous lower eyelid. Sirolimus associated eyelid edema is an important medication side effect for ophthalmic and eyelid specialists to consider when a patient with a history of organ transplantation presents with localized noninflamed eyelid edema. This edema can persist despite discontinuation of the medication. Surgical excision of the edematous eyelid can achieve good results.