The pharmacokinetics of baclofen is well delineated in subjects with normal kidney function (KF); however, pharmacokinetics data in patients with chronic kidney disease (CKD) are not and dosage recommendations remain empirical. The effects of CKD on baclofen pharmacokinetics were assessed through a multi-center, open-label, single 5-mg dose, pharmacokinetics study. The KF was measured as the creatinine clearance (CrCL) calculated with the Cockroft–Gault (C–G) equation or as the estimated glomerular filtration rate (eGFR) using subjects' CKD-EPI equation. Subjects were assigned to 1 of 4 groups based on their CrCL (>80 mL/min, 50–80 mL/min; 30–50 mL/min and <30 mL/min). Cmax was not statistically different between the groups, while AUC and T1/2el increased, and CL/F decreased, with increasing severity of CKD. Baclofen's oral clearance and CrCL were statistically significantly correlated, and the trend was the same when classifying subjects either with the CKD-EPI or C–G equations. Linear equations using KF as variable were set to recommend individual dose reduction in CKD patients. Results suggest a mean dose reduction of 1/3, 1/2, and 2/3 in patients with mild, moderate, and severe CKD respectively, in order to achieve baclofen exposure comparable to that observed in healthy subjects.