Objective To observe the effects of low-dose theophylline and tiotropium on lung function and quality of life in patients with mild-moderate stable chronic obstructive pulmonary disease (COPD) and evaluate its safety.Methods This was a randomized,parallel-group,controlled trial.A total of 115 patients with mild-moderate stable COPD were divided into tiotropium group (37 cases),slow-release theophylline group (40 cases) and the combination of slow-release theophylline and tiotropium group (38 cases) by random digits table method.Thirty-eight patients without cardiopulmonary diseases were enrolled in control group.Observation period was 12 months.The lung function,6 min walking test distance (6MWD),modified British Medical Research Council Scale (mMRC),and COPD assessment test (CAT) were monitored before treatment and after treatment for 12 months.Results Of 115 patients,107 patients (35cases in tiotropium group,36 cases in slow-release theophylline group and 36 cases in combination of slowrelease theophylline and tiotropium group) completed the study.No significant difference was found in spirometry parameters reflecting airflow limitation after 12 months treatment compared with that before treatment in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group (P ＞ 0.05),such as the percentage of forced expiratory volume in 1 second (FEV1) over the expected value (FEV1％) and FEV1/forced vital capacity (FVC).The percentage of mid expiratory flow over the expected value (FEF25～75％) was improved in all groups,but the increment of FEF25～75 ％ was much higher in tiotropium group and the combination of slow-release theophylline and tiotropium group than that in slow-release theophylline group:(39.23 ± 7.77)％,(39.99 ± 8.25)％ vs.(34.91 ± 9.50)％,there were significant differences (P ＜ 0.05).Similar changes were observed in mMRC and CAT score.There was significant difference in CAT score between tiotropium group,the combination of slow-release theophylline and tiotropium group and slow-release theophylline group:(14.34 ± 2.22),(14.39 ± 3.53) scores vs.(16.22 ± 3.35) scores,P ＜ 0.05.6MWD was no obvious change in tiotropium group,slow-release theophylline group and the combination of slow-release theophylline and tiotropium group before and after treatment.The use frequency of short-acting drugs bronchiectasis was the lowest in the combination of slow-release theophylline and tiotropium group,and only was (2.3 ± 1.4) times per week.Fourteen patients happened COPD exacerbations in slow-release theophylline group during 12 months treatment.The duration in slow-release theophylline group was more than that in tiotropium group and the combination of slow-release theophylline and tiotropium group:(9.76 ± 2.25) d vs.(7.85 ± 2.51),(8.29 ± 2.24) d,and there was significant difference (P ＜ 0.05).Conclusions For mild-moderate stable COPD patients,the quality of life and dyspnea scores are not improved significantly after treatment of low-dose slow-release theophylline,and the combination slow-release theophylline and tiotropium may be more beneficial and safe.