© 2015, Springer International Publishing Switzerland. Introduction: Dopaminergic agonists (DAs) are widely used to treat motor symptoms in Parkinson’s disease (PD). The differential effect of DAs on neuropsychiatric symptoms of PD has not been accurately studied. Materials and methods: We performed a prospective cross-sectional study of 515 non-demented PD patients receiving treatment with pramipexole [n = 250, monotherapy or with levodopa (l-dopa)], ropinirole (n = 150, monotherapy or with l-dopa), or l-dopa (n = 115, monotherapy); all formulations were immediate release. Neuropsychiatric disturbances were assessed through the Neuropsychiatric Inventory (NPI). Groups were matched in terms of age, education, sex, disease severity (Hoehn and Yahr), disease duration, executive function, total l-dopa daily equivalent dose, and concomitant psychotropic medications (antidepressants, anxiolytics and antipsychotic agents). Results: Patients on pramipexole showed significantly lower total NPI scores than patients on ropinirole (17.2 ± 11 vs. 20.9 ± 13, p = 0.015). Regarding the spectrum of neuropsychiatric symptoms, pramipexole was associated with significantly lower apathy scores than the l-dopa group (1.01 ± 1.7 vs. 1.87 ± 2.93, p = 0.02). The frequency of patients with clinically meaningful symptoms of apathy (NPI apathy scores ≥4) was significantly lower in the pramipexole group (11.2 %) than in the ropinirole (20.3 %) and l-dopa (23.8 %) groups (χ2 12.49, p = 0.002). No other significant differences were found in NPI subscores between groups. Conclusions: This is the first head-to-head comparative study of the effect of DAs on neuropsychiatric disturbances in PD that has controlled the sample for the most important confounding factors. In comparable groups of patients, the use of pramipexole seems to be associated with a lower frequency and severity of apathetic symptoms.