Objective: In this study, it was aimed to develop a novel reverse-phase liquid chromatography method for the ultra-sensitive determination of the antihypertensive drug captopril, using paracetamol, which is the common pain killer, as the internal standard. Optimization of all experimental conditions including composition of mobile phase, flow rate, and column temperature was carried out step by step, and the method validity of the developed method was examined according to international validation guidelines. Calibration range, linearity, the limit of determination, the limit of quantification, robustness, accuracy from commercial tablet samples, and method stability were examined in detail. In addition, the greenness profile for the developed method was assessed with the Green Analytical Procedure Index and Analytical Greenness Calculator techniques, which are frequently used in the literature. Material and Method: The chromatographic method was conducted with an XBridge C18 column (25 cm x 4.6 mm ID; 5 µm) packed with fully porous silica materials. All analyses were performed isocratically with a mobile phase containing acetonitrile:5 mM, pH 7.0 ammonium acetate solution (50:50, v/v) at a flow rate of 1.5 ml min-1. The injection volume was 5 μl, and the column was kept at 25°C in a column oven. The column eluate was monitored at 220 nm. Under optimized conditions, retention times of captopril, and paracetamol were approximately 1.59, and 2.0 min, respectively. Result and Discussion: This study described a fully validated, simple, sensitive, accurate, linear, precise, and reproducible reversed-phase liquid chromatography method for the determination of captopril in tablet samples. Under optimal experimental conditions, the linear range was found in the range of 0.5-200 µg ml-1 and the correlation coefficient was greater than 0.99. Method precision was acceptable, with coefficients of variation between 0.05% and 0.61%. In addition, as a result of the recovery studies carried out on the tablet samples, the accuracy was found to be within satisfactory limits between 99.45% and 102.55%. Moreover, the greenness profile of the developed method also showed that the method is environmentally friendly.