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New venues are currently being explored to predict disease progression in Parkinson's disease (PD), such as non-motor subtypes and models merging motor and non-motor symptoms (NMS). By involving a subgroup of 585 patients from the PRIAMO (Parkinson Disease Non-motor Symptoms) study, the present 24-month longitudinal prospective analysis aimed to demonstrate that urinary dysfunction is an early marker of higher motor and non-motor burden as well as lower health-related quality of life.Multivariable mixed-effect logistic regression models controlling for demographic and clinical variables showed that the following NMS domains were associated with urinary dysfunction: gastrointestinal [odds ratio (OR) 2.57, 95% confidence interval (CI) 1.67–3.97, P < 0.001], cardiovascular (OR 2.22, 95% CI 1.18–4.17, P = 0.013), skin (OR 1.81, 95% CI 1.06–3.08, P = 0.029), sleep (OR 2.06, 95% CI 1.34–3.16, P = 0.001), pain (OR 1.85, 95% CI 1.21–2.83, P = 0.004), fatigue (OR 2.40, 95% CI 1.56–3.68, P < 0.001), apathy (OR 2.79, 95% CI 1.72–4.52, P < 0.001) and respiratory (OR 1.82, 95% CI 1.02–3.23, P = 0.039). Analysis also demonstrated that urinary dysfunction was associated with higher motor disability (coefficient 1.73, 95% CI 0.68–2.78, P = 0.001) and lower health-related quality of life (coefficient −0.05, 95% CI −0.08 to −0.02, P < 0.001, and coefficient −3.49, 95% CI −5.21 to −1.77, P < 0.001) but not with more severe cognitive disability (coefficient −0.34, 95% CI −0.92 to 0.24, P = 0.251).This is the first prospective longitudinal study involving a large cohort of PD patients demonstrating the relevance of urinary dysfunction as an early marker of higher motor and non-motor disability as well as lower health-related quality of life. These findings support a role for urinary dysfunction as an early marker of more severe disease progression.