A reversed-phase liquid chromatography (LC) method with UV detection was developed and validated for the assay of N-acetylcysteine (NAC) in granules and effervescent tablets. The method involves the use of the same chromatographic conditions and avoids any derivatization step. The separation was done using a reversed-phase column LC-18, as the stationary phase, and a mixture of 0.05 M KH₂PO₄ and acetonitrile (95 : 5 v/v) containing 0.095% (v/v) of phosphoric acid, as the mobile phase. UV detection was performed at 214 nm and a linear response was observed over the concentration range between 10 and 50 μg mL⁻¹ of NAC. The method was revealed to be suitable and was successfully validated in accordance with the official guidelines for specificity, linearity (r = 1), detection and quantification limits (0.70 and 2.11 μg mL⁻¹), precision (RSD < 2%), accuracy (recovery > 97%), and robustness (RSD < 4%). Therefore, NAC can be assayed in granules and effervescent tablets using the same chromatographic conditions without derivatization.