The incidence of ALS in Wakayama Prefecture has been markedly higher than that elsewhere in the world. Recently, however, the incidence has gradually decreased, especially in men, and the age at onset has shifted to the elderly, indicating the possible role of exogenous factors in the development of ALS. To evaluate factors related to the disease, we conducted a retrospective study. This study examined 108 patients with definite ALS diagnosed according to El Escorial criteria and 302 neurological controls (older than 40 years old) consecutively admitted to Wakayama Medical Hospital between 1999 and 2004. Having past history of cervical spondylosis or spinal spondylotic myelopathy (CS/SSM) with/without surgical treatment, cervical MRI findings, history of bone fracture, and occupation at onset were compared between the ALS patients and the neurological controls. Among 108 ALS patients, 45.4% had past history of CS/SSM compared to 19.4% of the neurological controls (p<0.0001, OR: 3.725, 95% CI 2.173-6.387). Among the ALS patients, 13% had had surgical treatment for CS/SSM, which was significantly higher than the 4.3% of the neurological controls (p<0.003, OR: 4.333, 95% CI 1.647-11.401). Cervical MRI findings were classified into four grades according to the severity of canal narrowing and compression of the spinal cord. Regarding cervical MRI findings, the percentage of ALS patients who showed canal narrowing and compression of the spinal cord was significantly higher than that of the controls (ALS: 72.0%, the controls: 29.5%, OR: 4.799, 95% CI 2.65-8.70). Comparison of the occupation at disease onset revealed that primary and secondary industrial occupations significantly increased the risk of ALS (2.69, 95% CI 1.40-5.16, 2.81, 95% CI 1.45-5.46, respectively). Conversely, tertiary industrial occupations significantly decreased the risk of ALS (age- and sex-adjusted OR: 0.54, 95% CI 0.30-0.98). In conclusion, CS/SSM, surgical treatment for CS/SSM and occupation at onset are suspected to be risk factors for developing/triggering or worsening ALS.