A novel, rapid and sensitive liquid chromatography/tandem mass spectrometry method was developed and validated for the quantification of calcium channel antagonist lacidipine in human plasma. Carbamazepine was used as an internal standard. Analyte and the internal standard were extracted from human plasma by solid-phase extraction technique. The reconstituted samples were chromatographed on a C(18) column by using a mixture of acetonitrile-ammonium acetate buffer (5 mM) (80:20, v/v) as the mobile phase at a flow rate of 1.0 mL/min. The calibration curve obtained was linear (r(2)≥0.9990) over the concentration range of 0.05-12.5 ng/mL. The multiple reaction-monitoring mode was used for quantification of ion transitions at m/z 456.2/354.2 and 237.1/194.1 for the drug and the internal standard, respectively. The results of the intra- and inter-day precision and accuracy studies were well within the acceptable limits. A run time of 2.2 min for each sample made it possible to analyze more than 300 plasma samples per day. The proposed method was found to be applicable to clinical studies.