Background Complex medication schedules in Parkinson’s disease (PD) result in lower therapy adherence, which contributes to suboptimal therapy and clinical deterioration. Medication reminder systems might improve therapy adherence and subsequently improve symptoms of PD. This randomized controlled study assessed the effect of the electronic medication dispenser Medido on physical disability in PD, as a proxy for changes in therapy adherence.x Methods Eighty-seven patients were randomized into the Medido group or control group. The primary outcome of physical disability was measured by the AMC Linear Disability Scale (ALDS). Secondary outcomes were quality of life (QoL) (PDQ-39), health status (EQ5D-5L, VAS), non-motor symptoms (NMS-Quest), and QoL of the caregiver (PDQ-carer). Measurements were performed at baseline, and after 3 and 6 months follow-up. Results When using the Medido, a non-significant improvement of 3.0 points (95% CI -5.6;11.6) was seen in ALDS. The exploratory subgroup Hoehn & Yahr classification (H&Y) > 2.5 improved significantly on ALDS with 14.7 points (95% CI -28.5;-0.9, p = 0.029 for group x time interaction). QoL deteriorated with 1.0 point in PDQ-39 (p = 0.01 for group x time interaction) in favor of the control group. Non-significant differences were observed for VAS (0.4 points, p = 0.057) and NMS-Quest (1.3 points, p = 0.095) in favor of the Medido group. No changes over time were observed in EQ5D-5L and PDQ-carer. Conclusions Based on these data, no firm conclusion can be drawn, but use of the Medido medication dispenser may result in a clinical improvement of physical disability and seems particularly appropriate for more severe patients. Trial registration NTR3917. Registered 19 March 2013.