An accurate, sensitive and least time consuming reverse phase high performance liquid chromatographic (RP-HPLC) method for the estimation of ceftriaxone in the presence of statin drugs in formulation and human serum has been developed and validated. Chromatographic separation was conducted on prepacked Purospher Star, C18 (5 mm, 250 x 4.6 mm) column at room temperature using methanol:water:acetonitrile (70:15:20 v/v/v) as a mobile phase, pH adjusted at 2.8 with ortho-phosphoric acid and at a flow rate of 1.0 mL/minute, while UV detection was performed at 240 nm. The results obtained showed a good agreement with the declared content. The method shows good linearity in the range of 2.5-25 µg/mL with a correlation coefficient 0.9966 -0.9998 (inter-and intra-day RSD < 2 %).The limit of detection and quantification for ceftriaxone and statins in pharmaceutical formulation and serum were in the range 0.124 -1.006 µg/mL. Analytical recovery was >98.72 %. The proposed method may be used for the quantitative analysis of commonly administered statin's i.e. simvastatin, rosuvastatin atorvastatin and pravastatin alone or in combination with ceftriaxone from raw materials, dosage formulations and in serum. The established HPLC method is rapid, accurate and selective, because of its sensitivity and reproducibility.