Background: The aim of the present study was to evaluate the effect of second-hand smoke (SHS) and third-hand smoke (THS) on the incidence of postoperative emergence agitation (EA) in children. Methods: Six hundred children between the ages of 2– 12 were enrolled in this prospective cohort trial. The children were divided into three groups. Group I (Non-smoker; Children whose parents do not smoke and who are not regularly exposed to smoking environments), Group II (Second-hand smoker; Children whose parents smoke in their vicinity, causing them to inhale sidestream or mainstream smoke involuntarily), Group III (Third-hand smoker; Children exposed to pollutants from smoking parents via inhalation, ingestion or dermal contact, despite not directly inhaling sidestream or mainstream smoke). Emergence agitation, postoperative pain, shivering, nausea and vomiting were evaluated in the postanesthesia care unit. Watcha scale was used in the evaluation of emergence agitation. Results: In total, five hundred eighty-six patients completed the study, and the incidence of emergence agitation was higher in Group II (32.7%) and Group III (33.7%) compared to Group I (15.0%) (p < 0.001). The incidence of emergence agitation was dramatically increased in Group II and Group III compared to Group I (32.7% vs. 15.0%; odds ratio (95% confidence interval): 2.74 (1.68–4.48); p = 0.0001, and 33.7% vs. 15.0%; odds ratio (95% confidence interval): 2.87 (1.76–4.70); p < 0.0001, respectively). There was no difference between the groups in terms of postoperative pain, shivering, nausea and vomiting evaluated in the postanesthesia care unit. Conclusions: In conclusion, the results of the present study revealed that SHS and THS significantly increase the incidence of EA in children. Clinical Trial Registration: The trial was registered with the Australian New Zealand Clinical Trial Registry (ACTRN12619001359123).