To investigate longitudinal changes in the survival rate of patients with amyotrophic lateral sclerosis in Wakayama Prefecture, Japan, we made a retrospective hospital-based study of 454 patients diagnosed with motor neuron disease (MND) at Wakayama Medical University (WMU) Hospital between 1966 and 2005. Of the 454 patients, 240 who were born and who lived in Wakayama Prefecture were diagnosed with definite or probable ALS during this period, according to the El Escorial criteria. The clinical data of the 240 patients, including sex, birth date, birthplace, address, age at onset, initial symptoms, date when respiratory support was applied (tracheostomy, noninvasive positive pressure ventilation, or mandatory artificial ventilation), and date of death were reviewed retrospectively. The age at onset of patients who developed initial symptoms before 1990 was 53.4+/-10.6 (mean+/-S.D.) and that in 1990 or thereafter was 64.8+/-10.3, respectively, showing a significant difference (p<0.0001). Clinical duration was determined from onset to either date of death or initiation of respiratory support in this study. Survival rate was compared using the Kaplan-Meier method according to age at onset, sex, initial symptoms and year of onset. Mean age at onset shifted towards older age according to a later year of onset, due to the overwhelming senility rate in Wakayama Prefecture. Older onset patients had a significantly poorer survival rate than younger onset patients when it was compared based on 10-year age groups (log rank, p<0.0001). Male patients had a poorer survival rate than female patients (p<0.0001). ALS patients with bulbar palsy onset showed shorter clinical durations than those with lower leg onset (p<0.0071, Breslow-Gehan-Wilcoxon test). Patients over 70 years old more frequently showed bulbar palsy onset compared to those younger than 69 (p=0.003). In a comparison of year of onset before and after 1990, ALS patients after 1990 had characteristics of older age onset and shorter clinical duration, and more frequently showed bulbar palsy onset compared with those before 1990. These findings indicated that younger onset patients with ALS decreased after 1990 in Wakayama Prefecture and this might partly explain the recent decline of ALS incidence in Wakayama Prefecture. The shift of the mean age at onset to older age might be due to exogenous factors, including changes in lifestyle, food, and drinking water in this area. Bulbar palsy onset and age at onset were expected as predictors of the survival rate.