This study was performed to investigate the bioequivalence of cefuroxime axetil tablets between a generic test product (A) Zednad® Tablet (500 mg cefuroxime/ tablet, Diamond Pharma, Syria), and the Reference Product (B) Zinnat® Tablet (500 mg cefuroxime/tablet, GlaxoSmithKline, Saudi Arabia). The bioavailability study was carried out for 24 healthy male volunteers. The subjects received 1 Zednad® Tablet (500 mg/ tablet) and 1 Zinnat® Tablet (500 mg/tablet) in a randomized, two-way crossover design fashion on 2 treatment days, after an overnight fast of at least 10 h, with a washout period of 7 days. 24 volunteers plus 2 alternatives completed the crossover. The bioanalysis of clinical plasma samples was accomplished by HPLC method, which was developed and validated in accordance with international guidelines. Pharmacokinetic parameters, determined by standard non-compartmental methods, and ANOVA statistics were calculated using SAS Statistical Software. The significance of a sequence effect was tested using the subjects nested in sequence as the error term. The 90% confidence intervals for the ratio between the test and reference product pharmacokinetic parameters of AUC0→t, AUC0→∞, and Cmax were calculated and found to be within the confidence limits of 80.00 - 125.00% for AUC0→t, AUC0→∞ and Cmax. The study demonstrated that the test product (A) was found bioequivalent to the reference product (B) following an oral dose of 500 mg tablet. Therefore, the two formulations were considered to be bioequivalent.