Several environmental and life-style factors reported as possibly associated with ALS have been analysed in the present study, focusing on the two clinical onsets of ALS. A case-control study (77 cases and 185 controls) has been performed in the province of Rome in the period 2005-2006. Increased risks were observed in bulbar cases for former smokers (OR: 4.55, 90% CI 1.72-12.08) and more than 24 pack-years, compared with spinal cases for employment in the construction sector and professional exposure to building materials (OR: 5.27, 90% CI 1.15-24.12) and metals (OR: 2.94, 90% CI 1.20-7.21). Overall and bulbar cases showed an increased risk for consumption of cold cuts and a decreased risk for vegetables intake. Regarding head injuries, differences were observed if the last injury occurred in the age range of 30-40 years, among all (OR: 14.2, 90% CI 1.04-194.42) and bulbar (OR: 17.4, 90% CI 1.70-178.5) cases, and less than 30 years among spinal cases (OR: 7.13, 90% CI 1.34-37.94). Moreover, a risk for a time period of 11-30 years since the last head injury suffered was found in bulbar cases (OR: 3.51, 90% CI 1.03-11.95). Some of the hypothesized risk factors for ALS have been found positively associated in this study, with different patterns between bulbar and spinal ALS.