Despite recent interest in late-onset Huntington’s Disease (LoHD) phenotype, scarce evidence is available regarding it’s progression. This study aimed to investigate changes over time in clinical features in LoHD patients. This is a retrospective observational study on 99 LoHD (motor onset ≥60 years) and 854 patients with common-onset (CoHD, motor onset 30-59 years) from Enroll-HD PDS5, followed-up to 4 years. Linear mixed models were performed to evaluate differences between the two groups and the ‘time’ effect at three different timepoints: t0 (baseline), t1 and t2 (respectively, 2 and 4 years). Body Mass Index (BMI), Total UHDRS Functional Capacity (TFC) &Total Motor Score (TMS), Problem Behaviors Assessment (PBAs), MMSE and a short cognitive battery were examined at each timepoint. The results showed that 50.4% of CoHD patients were males, the mean age at baseline was 52.57±8.96 years, the mean CAGn on mutated allele was 43.50±2.47. LoHD patients were males in 41.4%; baseline mean age was 70.88±4.74 years, and mean CAGn was 40.83±1.31. In CoHD and LoHD, weight remained stable at t1 but significantly decreased at t2; motor performance significantly worsened at t1 and t2, and functionality scores lowered at both timepoints. Significant differences between groups emerged on many cognitive tasks, with LoHD showing less preserved cognitive status. Time effect emerged in most tests, with significant progressive worsening. At PBA-s, depression significantly reduced at t2 while apathy increased. No significant changes were detected in irritability and psychosis over time. In conclusion, the clinical progression of both groups is characterized by worsening in motor and cognitive performance and reduction in functionality over 2 and 4 years. Neuropsychiatric features follow different trajectories along HD course, deserving further exploration.