Randomized trials of adjunctive treatment of bacterial sepsis with polyclonal immunoglobulin show conflicting results. We performed a systematic review and a meta-analysis of the results of randomized trials that compared reductions in mortality rates in patient groups treated with polyclonal immunoglobulin versus either placebo or no treatment in addition to conventional treatment. High-quality trials had adequate concealment of allocation, were double-blinded and placebo-controlled, and made data available for intention-to-treat analyses. Twenty trials were included. Meta-analysis of all trials showed a relative risk of death with immunoglobulin treatment of 0.77 (95% confidence interval [CI], 0.68–0.88). High-quality trials (involving a total of 763 patients, 255 of whom died) showed a relative risk of 1.02 (95% CI, 0.84–1.24), whereas other trials (involving a total of 948 patients, 292 of whom died) showed a relative risk of 0.61 (95% CI, 0.50–0.73). Because high-quality trials failed to demonstrate a reduction in mortality, polyclonal immunoglobulin should not be used for treatment of sepsis except in randomized clinical trials.