A simple, precise and rapid, reversed phase-high performance liquid chromatography (RP-HPLC) method is developed for simultaneous determination of chlordiazepoxide and amitriptyline hydrochloride in tablet dosage forms. The HPLC conditions used are methanol: acetonitrile (75:25 v/v) mobile phase, Zodiac C18 column (250mm x 4.6mm x 5μm), pump pressure (9.5 MPa) and detection wavelength (221 nm). The measured elution times are 4.87±0.02 minutes for chlordiazepoxide and 7.38±0.02 minutes for amitriptyline hydrochloride, respectively. The method is validated for linearity range, recovery, robustness and sensitivity. Linearity is demonstrated for chlordiazepoxide and amitriptyline hydrochloride in the range 5-30 μg/mL (r2 = 0.9998) and 15-75 μg/ml (r2 = 0.9997). The mean recoveries ranged from 98.81-100.63% and 98.97-101.33% and the limit of detections (LOD) are 0.15 μg/ml and 0.5 μg/ml for chlordiazepoxide and amitriptyline hydrochloride, respectively. The proposed method proved to be specific, robust and accurate and has good signal to noise ratio with well resolved peaks for unambiguous determination of chlordiazepoxide and amitriptyline hydrochloride combination and in tablet dosage form.