Background & Objectives: Antibiotics are usually stable and biologically active. They have potential negative effects on the environment and organisms and cause drug resistance in humans. This study carried out to assess the performance of the Electro-Fenton process to remove Amoxicillin (AMX) from synthetic solution by using iron electrodes at different operating conditions.Methods: In present experimental study a Plexiglas cell (1.95 liter in volume) with two iron electrodes of 10×3×0.1 cm was used. Experiments were carried out at different conditions i.e. pH of 3 to 9, current density of 16.6 to 50 mAcm-2, 0.08 to 0.33 mole of H2O2 and initial amoxicillin concentration of 30 to 120 mg L-1 at reaction time of 10 and 120 min. AMX samples and total iron were measured using direct optical spectrometer at 294 nm and phenanthroline method at 510 nm, respectively.Results: The highest efficiency of 94% was observed at; initial pH=3, electrolyte of 2.5 g L-1, current density=50 mAcm-2, H2O2 concentration=0.16 M, initial amoxicillin concentration of 30 mg L-1 with a retention time of 120 minutes. The highest concentration of iron in the effluent was recorded as 10.9 mg L-1 for a reaction time of 80 min, current density of 41.6 mA.cm-2, pH=3, H2O2 concentration of 0.16 M and the amoxicillin concentration of 80 mg L-1.Conclusion: The Electro-Fenton method demonstrated acceptable removal efficiency using iron electrodes from synthetic effluent on a laboratory scale. However, the removal efficiency was unacceptable for amoxicillin initial concentrations higher than 50 mg L-1. But, industrial effluents usually contain much lower concentrations than that of tested levels.