Objectives: Workers in the mining industry in altitude are subjected to several risk factors, e.g., airborne silica and low barometric pressure. The aim of this study has been to assess the risks for this work category, evaluating single risk factors as airborne silica, altitude and work shift, and relating them with cardiovascular and ventilatory parameters. Material and Methods: Healthy miners employed in a mining company, Chile, working at varied altitudes, and subjected to unusual work shifts, were evaluated. Cardiovascular and respiratory parameters were investigated. Exposure to airborne silica was evaluated and compared to currently binding exposure limits. Results: At varied altitudes and work shifts, alterations emerged in haemoglobin, ventilation and respiratory parameters, related to employment duration, due to compensatory mechanisms for hypoxia. Haemoglobin increased with altitude, saturation fell down under 90% in the highest mines. The multiple linear regression analysis showed a direct relationship, in the higher mine, between years of exposure to altitude and increased forced vital capacity percent (FVC%), and forced expiratory volume in 1 s (FEV1). An inverse relationship emerged between forced vital capacity (FVC) and years of exposure to airborne silica. In the workplace Mina Subterrànea (MT-3600), statistically significant inverse relationship emerged between the Tiffeneau index and body weight. Conclusions: The working conditions in the mining industry in altitude appeared to be potentially pathogenic; further investigations should be realized integrating risk assessment protocols even in consideration of their undeniable unconventionality. Int J Occup Med Environ Health 2018;31(2):129–138