Asthma is a chronic disease due to inflammation of the airways of lungs that is clinically characterized by variablesymptoms including wheezing, coughing and shortness of breath. Angiotensin I-converting enzyme (ACE) plays a majorrole in fibrous tissue formation and is highly expressed in lungs. The main aim of this research work was to study the roleof ACE insertion/deletion (I/D) polymorphism, rs4646994, in asthma in Pakistani patients. A total of 854 subjects,including 333 asthma patients and 521 ethnically matched controls, were studied. The ACE (I/D) polymorphism wasgenotyped using polymerase chain reaction (PCR). Chi-square, Fisher’s exact and Hardy–Weinberg equilibrium testswere used to compare groups. Homozygous insertion genotype II ($p \ lt 0.0001$, $OR=3.38$) and insertion allele (I) wassignificantly more frequent in Pakistani asthmatics than in healthy controls ($p=0.0007, OR=1.40$). The ID genotype ($p \lt 0.0001$, $OR=0.43$) and the deletion allele (D) were associated with protection of disease in Pakistani patients($p=0.0007, OR=0.71$). These data suggest the involvement of ACE I/D polymorphism in asthma risk in the Pakistanipopulation. This marker may be an important indication in the molecular mechanism of asthma and can become a usefultool in risk assessment and help in designing strategy to combat disease.