Aim: The aim of the present study is to correlate and compare alpha-1 antitrypsin level in smoker and non smoker chronic obstructive pulmonary disease patients. Material and Methods: A comparative study was carried out in 200 subjects, more than 40 years of age and having chronic obstructive pulmonary disease for more than 1 year with a history of smoking at least 20 cigarettes per day (Group A) and without a history of smoking (Group B). Pulmonary function tests were used to diagnose the disease as per the Global Initiative for Chronic Obstructive Lung Disease (GOLD) classification. Alpha-1 antitrypsin level was done by turbidimetry method on fully auto analyzer I-Lab 650 (Instrumentation Laboratory, USA) at Clinical Biochemistry Section, Laboratory Services Sir Takhtsinhji Hospital, Bhavnagar. Statistical analysis was done by using unpaired t-test and Pearson’s correlation coefficient. Results: Results of present study shows that alpha-1 antitrypsin level was decreased in smoker chronic obstructive pulmonary disease patients (150.83±18.853) when compared to non smokers (183.97±29.383). There was statistically significant difference in alpha-1 antitrypsin level between the two groups with ‘p’ value of <0.0001. Pearson’s correlation test show negative correlation between smoker and nonsmoker chronic obstructive pulmonary disease patients. Conclusion: The values of serum alpha-1 antitrypsin levels were more significantly decreased in smokers indicating an important role of smoking in pathogenesis of chronic obstructive pulmonary disease. Alpha-1 antitrypsin can act as a predictor for future development of chronic obstructive pulmonary disease in smokers and in nonsmokers.