OBJECTIVE To estimate the summary effectiveness of different needle-stick injury (NSI)-prevention interventions. DESIGN We conducted a meta-analysis of English-language articles evaluating methods for reducing needle stick, sharp, or percutaneous injuries published from 2002 to 2012 identified using PubMed and Medline EBSCO databases. Data were extracted using a standardized instrument. Random effects models were used to estimate the summary effectiveness of 3 interventions: training alone, safety-engineered devices (SEDs) alone, and the combination of training and SEDs. SETTING Healthcare facilities, mainly hospitals PARTICIPANTS Healthcare workers including physicians, midwives, and nurses RESULTS From an initial pool of 250 potentially relevant studies, 17 studies met our inclusion criteria. Six eligible studies evaluated the effectiveness of training interventions, and the summary effect of the training intervention was 0.66 (95% CI, 0.50-0.89). The summary effect across the 5 studies that assessed the efficacy of SEDs was 0.51 (95% CI, 0.40-0.64). A total of 8 studies evaluated the effectiveness of training plus SEDs, with a summary effect of 0.38 (95% CI, 0.28-0.50). CONCLUSION Training combined with SEDs can substantially reduce the risk of NSIs.