Leukotriene A4 hydrolase (LTA4H) is associated with inflammation and emphysema. Nevertheless, clinical implications of LTA4H genetic polymorphism in chronic obstructive pulmonary disease (COPD) has been understudied to date. A prospective study was performed to investigate the clinical implications of LTA4H genetic polymorphism in patients with COPD. AA, GA, and GG types of genetic polymorphism of LTA4H were assayed in patients with COPD at the baseline. Then all patients were followed up for 12 months. At the baseline, the number of participants with AA, GA, and GG type of LTA4H rs7971150 were 22 (14.2%), 43 (27.7%), and 90 (58.1%) in the COPD group (n = 155), whereas 55 (36.7%), 38 (25.3%), and 57 (38.0%) in the control group (n = 150) (p = 0.001). During the follow-up, the variations with respect to forced expiratory volume in one second (FEV1), 6 min walking distance (6MWD), and BODE (body-mass index, obstruction, dyspnea, and exercise capacity) were similar between patients with AA and GA types, which were both lower than those of GG type. The patients with GG type had more hospitalizations than patients with AA (p = 0.001) and GA (p = 0.001) types, respectively. The cumulative hospitalization-free rate in patients with GG type was lower than those of patients with AA and GA types, respectively (p = 0.019). Compared with COPD patients with AA and GA types, patients with GG type were positively correlated with smoking, more hospitalizations, worse FEV1, 6MWD, and BODE index. The current study suggests that GG type of LTA4H is a predisposing factor in COPD development, functional decline, and exacerbation of patients with COPD.