The aim of this study was to determine if work at high altitude is associated with accelerated lung function decline and if smoking could further accelerate this decline. Subjects working at high altitude (3800 to 4500 m) in a gold mine on shift-rotation basis were included, and 7320 spirometry reports were obtained throughout a 4-yr observation period (2005-2009). Out of 3368 selected reports with acceptable quality, for 842 patients aged 38.9 ± 8.6 yr we analyzed annual decline in vital capacity (VC), forced vital capacity (FVC), and forced expiratory volume during the first second (FEV(1)). VC was reduced by 46.5 mL, FVC by 67.8 mL, and FEV(1) by 74.5 mL a year, greater than in historical controls. In those having initial FEV(1)/FVC below 70%, yearly VC decline was 59.4 mL, FEV(1) -58.6 mL. In long-term workers with no initial obstruction, FEV(1) declined slower (67.2 vs. 101.3 mL/yr (p < 0.001); but VC and FVC decline did not differ. Work at high altitude for years may be a factor that accelerates lung function decline, and the rate of decline along with confounding factors should be the subject of future studies.