A new clinical trial published in theJournal of the American Medical Associationrevealed that adding levodopa did not significantly improve motor function at 3 months when compared with placebo plus standard rehabilitation in patients undergoing inpatient rehabilitation for acute stroke. Levodopa has long been thought to improve dopaminergic signaling and stimulate neuroplasticity, potentially boosting recovery in patients with neurological damage. Despite its use in some rehabilitation programs, the evidence for its benefit after stroke has remained mixed. Thus, this trial which involved 610 patients with acute ischemic or hemorrhagic stroke and meaningful hemiparesis was conducted. Across 13 stroke units and 11 rehabilitation centers in Switzerland, the patients were randomized equally to receive either levodopa/carbidopa (100 mg/25 mg) or a placebo 3 times daily for 39 days. Both groups also received standardized, active, task-oriented rehabilitation. Enrollment began in June 2019, with the last patient completing follow-up in August 2024. The primary outcome measured motor recovery using the Fugl-Meyer Assessment (FMA) score, a standardized scale ranging from 0 to 100, where higher scores indicate better motor function. A difference of six points was considered clinically relevant. At 3 months, 582 patients were available for the primary analysis, as 28 participants had died. These results showed that patients in the levodopa group achieved a median FMA score of 68, while the placebo group scored 64. However, the adjusted mean difference between the groups was just −0.90 points, with no statistical significance (95% CI, −3.78 to 1.98; P = .54). This falls well below the threshold of clinical relevance, signaling that levodopa did not provide additional benefit compared with placebo. Both groups experienced a similar rate of serious adverse events, suggesting that levodopa was safe but not effective for this indication. Infections were the most frequent complication, by affecting 55 patients in the levodopa group and 44 in the placebo group. Other serious events were distributed almost evenly (126 in the levodopa arm vs. 129 in the placebo arm). Overall, the findings suggest that levodopa does not improve recovery when combined with standard rehabilitation after stroke. While the drug remains vital in treating Parkinson’s disease, its role in stroke recovery appears limited. Engelter, S. T., Kaufmann, J. E., Zietz, A., Luft, A. R., Polymeris, A., Altersberger, V. L., Wiesner, K., Wiegert, M., Held, J. P. O., Rottenberger, Y., Schwarz, A., Medlin, F., Accolla, E. A., Foucras, S., Kägi, G., De Marchis, G. M., Politz, S., Greulich, M., Tarnutzer, A. A., … Rosemeyer, H. (2025). Levodopa added to stroke rehabilitation: The ESTREL randomized clinical trial. JAMA: The Journal of the American Medical Association.https://doi.org/10.1001/jama.2025.15185