The highest burden of Chronic Obstructive Pulmonary Disease (COPD) occurs in low and middle income countries. Low cost oral medications, if effective, could enable affordable, accessible COPD treatment.In this randomised, 3 arm, double-blind, double dummy, placebo controlled study conducted in 37 centres in China, symptomatic patients with moderate/very severe COPD were randomised 1:1:1 to low dose (LD) theophylline 100 mg bd+prednisone 5 mg once daily; LD theophylline 100 mg bd+placebo once daily; or placebo bd+placebo once daily for 48 weeks. The primary endpoint was annualised exacerbation rate.1670 subjects were randomised, and 1242 completed the study (1142 with acceptable Week 48 data). Subjects (75.7% male) were mean age 64.4 years, with mean (sd) baseline post-bronchodilator Forced Expiratory Volume in 1 s (FEV1) 1.1 (0.4)L, 42.2% predicted and mean (sd) St Georges Respiratory Questionnaire (SGRQ) score 45.8 (20.1). There were negligible differences between annualised exacerbation rates across the three treatments, being 0.89 (95%CI=0.78-1.02) on Prednisone-LD Theophylline; 0.86 (0.75-0.99) on LD Theophylline plus placebo, and 1.00 (0.87-1.14) on double placebo. The Rate Ratio between the first and the pooled comparative arms was 0.96 (0.83-1.12), and for LD Theophylline+placebo versus placebo was 0.866, 95% CI 0.728; 1.029, p=0.101 and for LD Theophylline+Low dose oral Prednisone versus placebo was 0.895, 95% CI 0.755; 1.061, p=0.201. Secondary outcomes of hospitalisations, FEV1, SGRQ and COPD Assessment Test (CAT) score showed no statistically significant difference between treatment arms. Serious adverse events (SAEs) other than exacerbations were <2% and did not differ between the treatment arms.LD theophylline alone or in combination with prednisone did not reduce exacerbation rates or clinically important secondary endpoints compared to placebo.