INTRODUCTION:People with Parkinson's disease (PD) can be classified into tremor dominant (TD) and postural instability and gait difficulty (PIGD) subtypes; the latter group having more impaired gait and increased fall risk. While there is some evidence that anti-parkinsonian medication, levodopa, might not improve balance and gait control or reduce fall risk in the PIGD subtype, it is unclear whether the levodopa dosage intake affects gait stability. To address these issues, this study used accelerometry to compare gait stability: (i) during before and after levodopa intake between non-PIGD and PIGD subtypes; (ii) between individuals who took less or >750 mg of levodopa/day. METHODS:In 15 non-PIGD (Combination of 13 TD patients and 2 classified as indeterminate subtype) and 23 PIGD participants of similar mean (SD) age ((63.0 (7.6) versus 62.6 (10.0) years, respectively)) and disease-duration (8.9 (8.9) versus 11.3 (4.6) years, respectively), head and trunk stability during gait was examined using anteroposterior, vertical and mediolateral acceleration harmonic ratios (HRs). Participants were assessed before and after a levodopa dose, during typical "off" and "on" periods, respectively. RESULTS:Two-way analyses of variance (group × medication status) revealed that compared to the non-PIGD subgroup, the PIGD subgroup showed significantly worse head stability (lower anteroposterior HR) in the "off" state, and significantly worse pelvis stability (significantly lower mediolateral and vertical HRs) in the "on" state (p < 0.05 for both). Levodopa was effective in treating most of the disease-related impairments (not bradykinesia) in both groups, (p < 0.05) but improved gait stability (lowered pelvis mediolateral and vertical HRs) only in people with the non-PIGD subtype (p < 0.05) and those taking <750 mg of levodopa/day (p < 0.05). CONCLUSIONS:People with the PD PIGD subtype exhibit impaired gait stability that is not improved and frequently worsened by levodopa. New non-pharmaceutical approaches, technological (e.g. cueing) or exercise-based (e.g. balance training) are required to improve or compensate for mediolateral gait instability in this subtype and ultimately prevent falls.