Respiratory system complications and abnormalities are common in patients with amyotrophic lateral sclerosis (ALS) and respiratory failure remains the most common cause of death. Extensive epidemiological longitudinal data have documented the extent, magnitude, and clinical course of these abnormalities, but few studies have provided objective information that can have prognostic significance for individual patients. In this study, the reported data represent results from a retrospective review of the medical records of 153 patients with ALS cared for at a single institution (The Penn State Milton S. Hershey Medical Center) over a 50-month period. Medical information in relation to respiratory system abnormalities and complications including pulmonary function measurements was extracted for data analyses. The intent of this review of longitudinal data from a relatively large cohort of patients with ALS was to identify clinically relevant easily-identifiable objective information and clinical milestones that could have potential prognostic significance when applied to individual patients. Demographic data including gender, survival outcome, respiratory symptoms, age of disease onset, and age at death were similar to previously published epidemiological studies: mean age at ALS disease onset was 58.9+/-12.7 years, and mean age at death was 66.7+/-10.8 years. For 151 patients with available data, the incidence of study defined respiratory complications included infectious pneumonia 13 (9%), venothromboembolism 9 (6%), and tracheostomy and mechanical ventilation 6 (4%). For 139 patients with serial measurements of forced vital capacity (FVC), median values for calculated rate of decline in FVC was 97 ml/30 days (2.4% predicted/30 days); 25% of patients had FVC rates of decline less than 52 ml/30 days (1.4% predicted/30 days) and 25% had rates of decline greater than 170 ml/30 days (4.4% predicted/30 days). Stratifying patients into two distinct clinical subgroups based upon rates of decline in FVC less than or greater than the median value of 97 ml/30 days identified an apparent two-fold increase in survival duration for ALS patients with slower rates of pulmonary physiology deterioration when referenced to either date of dyspnea onset or time from bi-level positive airway pressure (BiPAP) initiation (2.0+/-1.4 vs. 1.0+/-0.8 years; 1.9+/-1.5 vs. 1.0+/-0.9 years, respectively). We concluded that the correlation between clinically defined milestones, most importantly onset of dyspnea, and the calculated rate of decline in FVC represent obtainable and objective measurements that predict the natural course of respiratory muscle dysfunction in patients with ALS and provide important prognostic information in relation to individual patient survival duration.