Background: Studies indicated that smoking alters the response to anesthetics and alters the outcome of perioperative care. A full understanding of the impact of smoking cessation to enhance surgical outcomes is pertinent. Purpose: This research aimed to compare perioperative cardiopulmonary complications in smokers and non-smokers during elective surgery under general anesthesia. We aimed to determine the incidence of complications in patients with a history of smoking, identify those at an increased risk, and assess the relationship between smoking duration and complications Methods: A total of 100 patients, comprising 50 smokers and 50 non-smokers, were enrolled in the study. Various parameters, including heart rate increase during intubation, severe coughing, bronchospasm, oral secretions, oxygen desaturation, reintubation, opioid antagonist use, pulmonary edema, and other cardiopulmonary events, were assessed perioperatively. Statistical analysis involved both continuous and categorical variables. For continuous variables, the Student’s t-test and the Mann–Whitney U test were used for normally and non-normally distributed data, respectively. For categorical variables, chi-squared tests were employed. Sub-group analysis assessed the influence of smoking duration on the measured parameters. Results: Smokers exhibited significantly higher incidences of severe coughing, heart rate elevation during intubation, and bronchospasm compared to non-smokers. Additionally, smokers experienced more pronounced oxygen desaturation throughout the perioperative period. Furthermore, a longer history of smoking was associated with an increased risk of complications, with individuals smoking for 10 or more years displaying a higher incidence of adverse events. Conclusion: Smokers, particularly those with extended smoking histories, are at an increased risk of cardiopulmonary complications during elective surgery under general anesthesia. Emphasizing preoperative optimization, meticulous airway management, and smoking cessation support is essential to mitigate these risks. The study underscores the significance of these measures for enhancing perioperative safety and calls for further research to explore the long-term impacts and patient satisfaction associated with these interventions. These steps are essential not only for perioperative care but also for long-term health benefits among this patient population.