Purpose: The most widely used methods of tattoo removal are lasers and Intense Pulsed Light (IPL). These modalities require multiple treatment sessions with varying degrees of success. Imiquimod (Aldara®, 3M) is a new immune response modifier medication that increases phagocytosis. We hypothesize that the combination of IPL and imiquimod would result in more efficient removal of tattoos. Methodology: An IRB approved study was performed using 24 patients separated into two groups. Both groups had their tattoos treated with the Vasculight IPL (Lumenis®). Immediately post-treatment either medication or vehicle control was applied and then reapplied each night for four weeks. This cycle was repeated a second time after three months. The clearance was judged by five plastic surgeons in a blinded fashion. Results: 23 of 24 patients completed the study. 8 of 11 imiquimod patients had complete or excellent clearance of their tattoo, while only 4 of 12 control patients obtained similar clearance. All patients in the control group had moderate to severe pigmentary and scarring changes to obtain clearance, while only 1 imiquimod patient had moderate hypopigmentation. Conclusion: Combined use of imiquimod with IPL increases the clearance of tattoos and reduces the side effects of scarring and pigmentary changes.