Hypertension and dyslipidemia are two of the most frequently co-occurring cardiovascular risk factors. The combined regimen of hydrochlorothiazide (HCTZ), rosuvastatin (ROS), and losartan (LOS) helped in the successful management of both conditions. This work's objective is to develop an eco-friendly, sensitive, simple, and reliable chromatographic method for the simultaneous estimation of HCTZ, ROS, and the LOS ternary mixture in their pure form, and pharmaceutical formulations. Utilizing sodium dodecyl sulphate (SDS) in combination with polyoxyethylene-23-lauryl ether (Brij-35) could be a greener option with minimal environmental impact in liquid chromatographic separation techniques. Therefore, a micellar HPLC protocol was optimized and validated employing a mobile phase comprising a mixture of micelles of SDS (0.15 mol L−1 ) and Brij-35 (0.03 mol L−1 ) with 0.01 M monobasic potassium phosphate buffer, pH 3.5. The cited drugs were detected at 230 nm within five minutes, using a symmetry RP-C18 column, an isocratic elution mode, and a flow speed of 1 mL min−1 . Method validation was successfully performed as stated by ICH. The suggested HPLC approach was effectively applied to determine the mentioned drugs in three pharmaceutical preparations. It was also employed for monitoring their in vitro release pattern using two innovator tablet formulations, applying the USFDA guidelines. The applied procedure was evaluated and compared with previously published HPLC approaches using various metrics, including the Eco-Scale Scoring method (AES), the Green Analytical Procedure Index (GAPI), and the Analytical Greenness Calculator (AGREE) for greenness, the most current Blue Applicability Grade Index (BAGI) for blueness, and the more inclusive RGB 12 algorism for whiteness assessment