Study objective The use of prophylactic antibiotics in patients with simple hand lacerations is controversial. This evidence-based emergency medicine review evaluates the existing evidence about the utility of prophylactic systemic antibiotics for prevention of infection in patients with simple hand lacerations. Methods MEDLINE, EMBASE, the Cochrane Library, and other databases were searched. Studies were selected for possible inclusion in the review if the authors stated that they had randomly assigned patients to an antibiotic treatment group or a control group and if they followed them up for the occurrence of infection. They also had to describe a reasonable method of wound cleaning for all subjects, repair the wounds, and exclude hand lacerations that involved special tissues such as bone, tendons, nerves, or large vessels. Standard criteria to appraise the quality of published trials were used. Results Four randomized trials met the inclusion criteria, of which 3 met minimally acceptable quality standards. Relative risks of infection after antibiotic use were 1.05 (95% confidence interval [CI] 0.09 to 11.38), 0.73 (95% CI 0.37 to 1.46), and 1.07 (95% CI 0.07 to 16.80) for the 3 included studies. In these trials, the differences in infection rates between antibiotic and control groups failed to reach statistical significance. Conclusion No convincing trend toward either benefit or harm from administration of antibiotics for uncomplicated hand lacerations is apparent. Clinical judgment based on individual cases should be used in such settings.