Complicated upper urinary tract infection (UTI) is a significant cause of infectious morbidity and in-hospital antibiotic therapy. However, the use of first-generation cephalosporins in this scenario is not clearly defined.To evaluate the efficacy and safety of first-generation cephalosporins for community-acquired complicated upper UTI in adults requiring hospital care.Systematic review by searching electronic databases (MEDLINE, Embase, CENTRAL) and trials registers. The articles were then screened and the references were selected, data was extracted, and risk of bias assessment was conducted. The results are presented in a narrative synthesis.Seven randomized clinical trials were included. We did not identify statistically significant differences when comparing first-generation cephalosporins with other antimicrobials for outcomes of clinical cure, length of hospital-stay, and reinfection. However, a lower probability of microbiological cure and a higher probability of relapse was identified in the first-generation cephalosporin group in 3 of 7 studies and in 2 of 5 studies, respectively. No serious adverse effects were reported.First-generation cephalosporins could be a potential therapy in this setting, nevertheless the low quality of evidence for analyzed outcomes should be considered because of the limitations of the risk of bias assessment and its inaccuracy. It is essential to carry out comparative studies in which the benefits and harms of these antibiotics are evaluated.