A systematic review and meta-analysis of randomised controlled trials was performed in order to study the effectiveness of prophylactic treatment regimens in preventing secondary cases of meningococcal disease (i.e., those contracted after contact with a person with meningococcal disease) and in eradicating Neisseria meningitidis from the pharynx of healthy colonised individuals. The Medline, Embase, and Lilacs databases, the Cochrane Library, and the references of all studies identified were systematically searched for relevant trials. Two reviewers independently applied selection criteria, performed quality assessment, and selected data. Relative risks were pooled using a fixed effects model unless heterogeneity assessed by the I2 statistic and chi-square test was found. In such cases, a random effect model was used. There were no cases of meningococcal disease following treatment with antibiotics or placebo, thus effectiveness regarding prevention of future disease could not be directly assessed. Compared with placebo, ciprofloxacin (RR = 0.04; 95%CI, 0.01-0.12), rifampin (RR = 0.17; 95%CI, 0.12-0.24), minocycline (RR = 0.30; 95%CI, 0.19-0.45), and penicillin (RR = 0.47; 95%CI, 0.24-0.94), proved effective at eradicating Neisseria meningitidis 1 week after treatment. After 1-2 weeks, only ciprofloxacin (RR = 0.03; 95%CI, 0.00-0.42) and rifampin (RR = 0.20; 95%CI, 0.14-0.29) still proved significantly effective when compared with placebo. Rifampin continued to be effective (RR = 0.24; 95%CI, 0.16-0.37) compared with placebo until up to 4 weeks post treatment. Rifampin was the only drug to which resistance developed. Given that the use of rifampin in an outbreak setting might lead to the circulation of isolates resistant to rifampin, the use of ciprofloxacin and ceftriaxone should be considered.