The present method describes the development of a validated RP-HPLC method for determination of ceftaroline fosamil in presence of its degradation products or other pharmaceutical excipients. The drug substance was subjected to stress conditions of acid, alkali, and oxidative and thermal degradation studies. Separation was carried out on a C-18 X-terra column (Waters Corporation, 250 mm × 4.6 mm I.D.; particle size 5 μm) using 40 : 30 : 30 [buffer : acetonitrile : methanol] as mobile phase at a flow rate of 1.0 ml/min. UV detection was performed at 242 nm. The method was validated with respect to specificity, selectivity, linearity, accuracy, precision, and robustness. The assay method was found to be linear in the range of 40 to 120 μg/mL with a correlation coefficient of 0.9999. The percentage recovery of active pharmaceutical ingredient from parenteral dosage form ranged from 99.5 to 100.2%. The method precision for determination of ceftaroline was below 0.85%. The results showed that the developed RP-HPLC method is suitable for determination of ceftaroline fosamil in bulk as well as stability samples of pharmaceutical dosage forms containing various excipients.