<sec><title>BACKGROUND</title>Severe exacerbation is the predominant cause of COPD hospitalisation. We investigated sex-specific risk factors of severe exacerbation and explored the potential interactions of regions, smoking status, and age.</sec><sec><title>METHODS</title>The present study included 13,641 males and 13,051 females with spirometry-defined COPD at baseline from the China Kadoorie Biobank. Hazard ratios (HRs) and 95% confidence intervals (CIs) of risk factors with severe exacerbation were estimated using the Cox models.</sec><sec><title>RESULTS</title>During a median of 11.5 years follow-up, 5,967 cases of COPD hospitalisation were recorded. GOLD (Global Initiative for Obstructive Lung Disease) stage, tobacco smoking, and underweight were positively associated with COPD hospitalisation in both sexes. Stronger associations were observed in females than in males; the corresponding HRs for males and females were respectively 1.87 (95% CI 1.73-2.03) and 2.47 (95% CI 2.24-2.72) for a history of respiratory diseases and 1.46 (95% CI 1.33-1.60) and 1.65 (95% CI 1.46-1.87) for coughing frequently and coughing up sputum after getting up in the morning for ≥3 months. Higher risks were found among urban residents, non-current smokers, and patients <60 years old.</sec><sec><title>CONCLUSIONS</title>Our findings may help clinicians and the public to identify COPD patients at high risk of exacerbation requiring hospitalisation and take targeted measures in time.</sec>.