Background People with Parkinson disease (PD), even in the presence of symptomatic relief from medical, surgical, and rehabilitative interventions, face a persistent worsening of disability. This disability is characterized by diminished quality of life, reduced functional mobility, declining performance in activities of daily living and worsening neurological impairments. While evidence has emerged supporting the clinically meaningful benefits of short-term exercise programs on these underlying factors, assertions regarding the effects of sustained programs of exercise and physical activity on the trajectory of disablement in PD are made in the absence of direct evidence. Indeed, the natural decline in quality of life and functional mobility in people diagnosed with PD is poorly understood. Moreover, outcome measures commonly used in clinical exercise trials typically do not capture the full spectrum of disability as defined by the World Health Organization (WHO). Methods/Design The objective of this multicenter prospective study will be to examine the 2-year trajectory of disablement in a cohort of persons with PD. Two hundred sixty participants will be recruited to produce an expected final sample size of 150 individuals. Participants will be included if they are greater than 40 years of age, have a neurologist confirmed diagnosis of idiopathic PD, and are at Hoehn and Yahr stages 1 through 4. Data will be collected every 6 months during the study period. Primary outcome measures reflecting a broad spectrum of disablement will include, but will not be limited to, MDS-UPDRS, Timed Up and Go, Berg Balance Test, Nine Hole Peg Test, PDQ-39, and directly monitored ambulatory activity. Self-reported exercise and physical activity data also will be recorded. Statistical analyses will be used to characterize the trajectory of disablement and examine the influence of its underlying contributing factors. Discussion Tertiary prevention is an important component of contemporary healthcare for individuals living with degenerative disease. For individuals with PD, there is growing recognition that exercise and/or physical activity efforts to slow the rate of functional mobility decline, in particular, may be critical for optimizing quality of life. By describing the natural trajectory of disablement, exercise habits, and physical activity in a cohort of persons with PD, this investigation will establish an important foundation for future intervention research. Specifically, through the evaluation of the influence of sustained exercise and physical activity on disablement, the study will serve as a preliminary step toward developing a randomized controlled trial of long-term exercise in persons with PD.