BACKGROUND: Although currently not authorized in many countries, medical-grade silicone (MGS) injections have been used for 50 years. Sometimes chronic and severe adverse effects refractory to usual therapy other than corticosteroids appear. OBJECTIVE: To evaluate the effectiveness of tacrolimus in the treatment of refractory cases of late-onset adverse effects related to MGS injections. METHODS: Case-series study of seven patients with late-onset adverse effects related to MGS injections. Cases had been treated with a mean of six drugs with poor response before low-tacrolimus dose was introduced. Patients who had received MGS injections with immediate adverse effects or drug responsiveness were excluded. Patients underwent clinical management and follow-up. RESULTS: Average latency period to onset of symptoms was 65 months (range: 6-144 months). Large, tender, inflammatory nodules; plaques; angioedema; and severe panniculitis were commonly seen. An average of 18 months after tacrolimus administration, five patients were experiencing mild, sparse bouts of inflammatory processes, including nodules, plaques, angioedema, and panniculitis. that were rapidly reversible, and two were in remission. No side effects related to tacrolimus had appeared. CONCLUSION: Tacrolimus is an effective and well-tolerated drug in cases of severe and refractory late-onset inflammatory reactions, including large panniculitis, that complicate silicone gel injections. © 2011 by the American Society for Dermatologic Surgery, Inc. Published by Wiley Periodicals, Inc.