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Context: Although the role of proteinase/antiproteinase imbalance in chronic obstructive pulmonary disease (COPD) due to tobacco is well established, information in COPD due to nontobacco etiology is sparse. Aims: To assess the variability in metalloproteinase activity in COPD related to tobacco and nontobacco causes. Settings and Design: This is a hospital-based, prospective, observational study. Subjects and Methods: Serum matrix metalloproteinase-9 (MMP-9) and tissue inhibitor of metalloproteinases-1 (TIMP-1) were estimated in 200 subjects divided equally into four groups, i.e. COPD in tobacco smokers, COPD in nonsmokers but with exposure to biomass-related indoor air pollution, smokers without COPD, and nonsmoking healthy controls. Anthropometric skinfold measurements, quality of life (QOL) using St. George Respiratory Questionnaire, and exercise capacity using the 6-min walk test (6-MWT) were carried out. Groups were compared using analysis of variance and Kruskal–Wallis plus Mann–Whitney U-test to assess differences between groups. The Chi-square and Fisher's exact tests were used to evaluate associations among categorical variables. Spearman's rank correlation was calculated to assess the correlation between data. Results: Patients with COPD due to either tobacco or nontobacco etiology were older, more malnourished, had worse QOL, and poorer exercise capacity compared to non-COPD subjects. Triceps, subscapular, and suprailiac skinfold thicknesses were less in smokers with COPD than biomass-related COPD. MMP-9 and TIMP-1 levels were similar across all groups. TIMP-1 significantly correlated with 6-MWT among all groups. Conclusions: The protease-antiprotease balance in COPD is similar irrespective of the presence or absence of tobacco exposure but is related to poor exercise capacity.