A specific, accurate, precise, and reproducible liquid chromatographic method has been developed and validated for the estimation of acamprosate calcium and baclofen in combination. The separation was achieved using stationary phase Phenomenex C18 column (150 mm× 4.6 mm.) in isocratic mode, with mobile phase containing 0.05 M potassium dihydrogen orthophosphate buffer (pH 7) : acetonitrile (10:90 V/V), at a flow rate of 1.0 mL/min and effluents were monitored at 210 nm. The retention time of acamprosate calcium and baclofen were found to be 1.9 min and 5.3 min, respectively. The linearity for acamprosate calcium and baclofen were in the range of 2-64 µg/mL and 1.2- 38.4 µg/mL, respectively. The method was validated as per ICH guideline. The recoveries of Acamprosate calcium and baclofen were found in the range of 98.90 - 100.13 % and 98.60 -100.02 %, respectively. The method was successfully applied for the determination of both the drugs in combination.