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Background & Objective: Pyelonephritis is one of the common disease during pregnancy. The aim of this study was assess the effect of cefteriaxone therapy versus cefteriaxone therapy in acute pyelonephritis in patients admitted in high risk pregnancy ward in Fatemieh hospital. Materials & Methods: This is a clinical trail study in pregnant patients with acute pyelonephritis that selected randomized in two therapeutic group. In one group 2 gr cefazoline was injected per 6 hrs and in another group 1 grcefteriaxone injected daily. the treatment continued until disappear of clinical symptoms and if the symptoms still persisted, after 72 hrs, the second line (Gentamycine) be added and then two groups for 7-10 days discharged with oral antibiotic, which determined by antibiogram. The patients were recommended to return during one week to 10 days after end of the period of treatment, to follow and doing urinary analysis and urine culture. Results: Cure in cefazoline group was 86.7% and recurrence was 13.3% and cure in cefteriaxone group was 83.3% and recurrence was 16.7%. There was not any significant differences between two group. Conclusion: This study showed that, the effect of cefteriaxone is the same as cefazoline in acute pyelonephritis in pregnancy.