Lymphoceles are common in renal transplant recipients who receive sirolimus (SRL). However, a recent MEDLINE search revealed no reports of lymphedema related to SRL. We describe three cases of lymphedema that resolved or improved on discontinuation of SRL. No other likely causes of lymphedema were discovered. Recognizing the association may lead to early discontinuation of SRL, which may prevent permanent disfigurement. It may also prevent unnecessary investigations. The mechanisms of this phenomenon are not clear. We hypothesize that increased lymph flow along with disrupted lymphatics in the affected extremities may explain this complication of SRL. Further studies are necessary to confirm our findings.