Background: Spasticity is a common feature of Upper Motoneuron Syndrome and is frequently treated with intrathecal baclofen (ITB) when oral therapy is ineffective or poorly tolerated. Different baclofen formulations are available for intrathecal use, but evidence regarding their clinical equivalence in patients requiring high daily doses remains limited. Methods: Thirty adult patients (mean age 37 ± 5.8 years) receiving long-term ITB therapy were switched from four vials of baclofen 10 mg/5 mL to a single vial of baclofen 40 mg/20 mL, while maintaining the same total drug amount and reservoir concentration. Patients were divided into two groups: in 15 patients, the daily baclofen dose was maintained unchanged, while in the remaining 15 patients a 10% dose reduction was attempted. Clinical outcomes were assessed at baseline and during follow-up using validated scales for spasticity, pain, and functional status. Results: In patients with unchanged daily dosing, no clinically relevant differences were observed in spasticity, pain, or functional independence after switching formulation, supporting clinical equivalence between the two preparations. Conversely, the 10% dose reduction proved clinically unsustainable in patients requiring high daily doses and required restoration of baseline dosing in all cases. No adverse events or formulation-related complications were observed. Conclusions: Switching to baclofen 40 mg/20 mL is safe and clinically equivalent to the conventional 10 mg/5 mL formulation when the daily dose is maintained unchanged. Dose reduction appears unsuitable in patients requiring high daily intrathecal baclofen doses.