Hyperhomocysteinaemia is associated with chronic obstructive pulmonary disease. However, the relationship between plasma homocysteine levels and spirometric measures has not been investigated in a general population. We aimed to determine whether homocysteine levels are predictive for a rapid decline in lung function among healthy current smokers. Blood sampling and spirometry were performed on subjects participating in a community-based annual health check in Takahata, Japan, from 2004 to 2006 (n=3257). Spirometry was re-evaluated in 147 male current smokers in 2009. On initial assessment, forced vital capacity (FVC) % predicted and forced expiratory volume in 1 s (FEV1) % predicted correlated inversely with homocysteine levels and were predictive for homocysteine levels, independent of various clinical factors. Homocysteine levels were higher in subjects with restrictive, obstructive or mixed ventilatory disorders. In addition, homocysteine levels were higher in subjects with mixed ventilatory disorders, compared with restrictive or obstructive disorders. On follow-up, subjects showing a decline in FEV1 had higher homocysteine levels than those who did not. Logistic regression analysis indicated that homocysteine levels were predictive for a decline in FEV1. FVC % pred and FEV1 % pred were significantly associated with homocysteine levels, and hyperhomocysteinaemia predicted the annual rate of decline in FEV1 among male smokers.