This study aimed to demonstrate interchangeability between 2 lornoxicam tablet formulations under fasting conditions among Mediterranean Arabs by using a newly validated high-pressure liquid chromatography–tandem mass spectrometry method. A single-oral solid dosage form (8 mg/tablet), randomized, open-label, 2-way crossover study was conducted on 30 healthy male volunteers. Blood samples were collected prior to dosing and over a 24-hour period, and the washout period was 9 days. Statistical comparison of the main pharmacokinetic parameters showed no significant difference between generic and branded products. The point estimates (ratios of geometric mean %) were 90.91, 96.34, and 94.86 for Cmax, AUC0–last, and AUC0–∞, respectively. The 90% confidence intervals were within the predefined limits of 80.00%–125.00%, as specified by the international guidelines. This study showed that both formulations met the regulatory criteria for bioequivalence.