BACKGROUND Despite the high incidence of acute pyelonephritis in the community setting, there is no consensus on the optimal duration of treatment. A potential reduction in the duration of the administered antibiotic regimens could contribute to avoiding further development of antimicrobial resistance. OBJECTIVE The aim of this meta-analysis was to compare short-course (7- to 14-day) with long-course (14- to 42-day) treatment with the same antibiotic regimens, in terms of the effectiveness and tolerability, in acute pyelonephritis. METHODS We searched PubMed, Cochrane Central Register of Controlled Trials, and SCOPUS (January 1966-March 2008) to identify and extract data from randomized controlled trials (RCTs) comparing the effectiveness and toxicity of short- versus long-course regimens. Additionally, references of studies were searched. A publication was included if: it was an RCT; involved adult and/or adolescent patients with acute pyelonephritis; compared regimens with the same antibiotic, at the same daily dosage, that were administered for differing durations (a short course and a long course lie, no absolute time cutoff (in days) was employed; rather, the duration of one regimen compared with another defined short- vs long-course]); and reported data regarding clinical success, bacteriologic efficacy, relapses, recurrences, and adverse events and/or patient withdrawals due to adverse events. Trials with a mixed population, including patients with acute pyelonephritis as a subset, were also included in the meta-analysis. Efficacy was assessed by evaluating clinical success, defined as resolution of symptoms and signs at the test-of-cure visit, and bacteriologic efficacy, defined as yielding sterile urine cultures or positive cultures with <10(3) colony-forming units per milliliter of urine at the test-of-cure visit. Tolerability was assessed by extracting data for adverse events. RESULTS According to our initial search, 205, 136, 179, and 73 potentially relevant articles were retrieved from PubMed, Cochrane Central Register of Controlled Trials, SCOPUS, and references of evaluable trials, respectively. Four RCTs were eligible for inclusion in the meta-analysis. Significant differences were not found between the short- and long-course treatment of acute pyclonephritis in terms of clinical success (odds ratio [OR], 1.27; 95% CI, 0.59-2.70), bacteriologic efficacy (OR, 0.80; 95% CI, 0.13-4.95), and relapse (OR, 0.65; 95% CI, 0.08-5.39). Also, significant differences were not found between the short- and long-course treatments regarding adverse events (OR, 0.64; 95% CI, 0.33-1.25), withdrawals due to adverse events (OR, 0.65; 95% CI, 0.28-1.55), and recurrences (OR, 1.39; 95% CI, 0.63-3.06). CONCLUSIONS This meta-analysis failed to identify any significant differences, with regard to effectiveness and tolerability, between short- and long-course treatment with the same antibiotic.