Background: E-cigarettes, nicotine transdermal patches, and nicotine chewing gum are occasionally used as cigarette replacements by patients, but it is unknown if their use is a safe alternative to smoking in the perioperative period. Methods: All patients undergoing major surgery at a single outpatient ambulatory surgery center for a 5-year period were tested for urine cotinine, a nicotine metabolite, the day of surgery. Patients were divided into 4 groups: never smoked (group A), quit smoking with negative urine test (group B), continued to smoke (group C), and quit smoking with positive urine test (group D). Statistical significance of complications among groups was tested using right tailed chi-square test and point biserial correlation coefficient calculations. To control for confounding factors, age and BMI of each group were compared using unequal sample size and variance t tests. Results: Four hundred seventy patients were included in the study. Patient count in each group was group A n = 380, group B n = 48, group C n = 32, and group D n = 10. Complication frequency was as follows D > C > A > B. Statistically significant differences were observed between D + C (cotinine positive) and A + B (cotinine negative) P = 0.0001 and between D (nicotine replacement) and B (nicotine abstinence) P = 0.00026. There was neither statistical difference between groups A and B, nor C and D. Conclusions: Nicotine replacement carries similar risks as continued smoking and is not as safe as abstinence in the perioperative period in plastic surgery patients. Importantly, patients who stopped smoking for the surgery had equivalent risk for postoperative complications as patients who had never smoked.