INTRODUCTION: The detrimental health effects of smoking tobacco are well known. Smoking tobacco increases the risks of many post-operative complications, many of which are germane to plastic surgery. The use of non-tobacco nicotine sources has proliferated in the hope that non-smoking delivery methods are safer than smoking; however, there is little data to support or refute this theory.1–4 METHODS: 5 year prospective study, (1/1//2012-12/2016). We informed patients that they should not smoke for 4 weeks before and 6 weeks after their surgery date. Each patient consented to study and allowed their urine to be tested the day of surgery. The patients were encouraged to stop all nicotine use, but if necessary, non-smoked delivery systems (ie transcutaneous patch, chewing gum) would be tolerated. The urine cotinine level was measured in patients undergoing major flap surgery or having general anesthesia. Patients were followed for 6 weeks to monitor for post-operative complications. Post-operative complications included any unplanned outcome requiring medical attention including but not restricted to infections, wound healing problems, unanticipated return to the operating room, etc. We then divided the patients into four groups: non-nicotine users (in the past year), smokers with negative urine test, smokers with positive urine test and non-smoked nicotine users. RESULTS: A total of 340 patients were tested. As expected non-nicotine users (n=264), had the lowest rate of complications at 18% (48). Tobacco smokers that tested positive (21) had the highest complication rate at 28.6% (6), while those testing negative (41) had rate of 19.5% (8) similar to non-smokers. Of note, patients using non-smoked nicotine source (14), developed the highest rate of complications 42.9% (6). Analysis of variance test, p-value of 0.26. CONCLUSION: There is evidence that even when administered through non-smoked methods nicotine does increase the risk of post-operative complications. The increased complication rate in non-smoked nicotine users may be related to higher nicotine blood levels, as it is possible that patches, chewing gum and vaporized usage encourages greater consumption. Given the increasing usage of non-smoked nicotine sources and the perception that the product offers a safe alternative to traditional tobacco use, further studies should be undertaken to better understand clinical implications of usage in aesthetic and plastic surgery. A larger study size could allow for data to reach statistically significant level. Reference Citations: 1. PDE-5 inhibition improves skin flap viability in rats that are exposed to nicotine. Shah A, Pfaff MJ, Assi R, Wu W, Steinbacher DM. Microsurgery. 2014 Jul;34(5):390–7. 2. The effect of hyperbaric oxygen therapy on the survival of random pattern skin flaps in nicotine-treated rats. Selçuk CT, Kuvat SV, Bozkurt M, Yaşar Z, Gülsün N, Ilgezdi S, Ula M, Ozalp B. J Plast Reconstr Aesthet Surg. 2012 Apr;65(4):489–93. 3. Impact of nicotine replacement therapy on postoperative mortality following coronary artery bypass graft surgery. Paciullo CA, Short MR, Steinke DT, Jennings HR. Ann Pharmacother. 2009 Jul;43(7):1197–202. 4. The association of nicotine replacement therapy with mortality in a medical intensive care unit. Lee AH, Afessa B. Crit Care Med. 2007 Jun;35(6):1517–21