Objective : To compare the efficacy and safety of short-course intravenous levofloxacin (LVFX) 750 mg with a conventional intravenous/oral regimen of LVFX 500 mg in patients from China with complicated urinary tract infections (cUTIs) and acute pyelonephritis (APN). ; Methods : This was a prospective, open-label, randomized, controlled, multicenter, non-inferiority clinical trial. Patients with cUTI and APN were randomly assigned to a short-course therapy group (intravenous LVFX at750 mg/day for 5 days) or a conventional therapy group (intravenous/oral regimen of LVFX at 500 mg/day for 7–14 days). The clinical, laboratory, and microbiological results were evaluated for efficacy and safety. ; Results : The median dose of LVFX was 3555.4 mg in the short-course therapy group and 4874.2 mg in the conventional therapy group. Intention-to-treat analysis indicated the clinical effectiveness in the short-course therapy group (89.87%, 142/158) was non-inferior to that in the conventional therapy group (89.31%, 142/159). The microbiological effectiveness rates were also similar (short-course therapy: 89.55%, 60/67; conventional therapy: 86.30%, 63/73; p > 0.05). There were no significant differences in other parameters, including clinical and microbiological recurrence rates. The incidence of adverse effects and drug-related adverse effects were also similar for the short-course therapy group (21.95%, 36/164; 18.90%, 31/164) and the conventional therapy group (23.03%, 38/165; 15.76%, 26/165). ; Conclusion : Patients with cUTIs and APN who were given short-course LVFX therapy and conventional LVFX therapy had similar outcomes in clinical and microbiological efficacy, tolerance, and safety. The short-course therapy described here is a more convenient alternative to the conventional regimen with potential implication in anti-resistance and cost saving.