BACKGROUND Recent studies have shown that using no-touch disinfection technologies (ie, ultraviolet light [UVL] or hydrogen peroxide vapor [HPV] systems) can limit the transmission of nosocomial pathogens and prevent healthcare-associated infections (HAIs). To investigate these findings further, we performed a systematic literature review and meta-analysis on the impact of no-touch disinfection methods to decrease HAIs. METHODS We searched PubMed, CINAHL, CDSR, DARE and EMBASE through April 2017 for studies evaluating no-touch disinfection technology and the nosocomial infection rates for Clostridium difficile, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant enterococci (VRE), and other multidrug-resistant organisms (MDROs). We employed random-effect models to obtain pooled risk ratio (pRR) estimates. Heterogeneity was evaluated with I2 estimation and the Cochran Q statistic. Pooled risk ratios for C. difficile, MRSA, VRE, and MDRO were assessed separately. RESULTS In total, 20 studies were included in the final review: 13 studies using UVL systems and 7 studies using HPV systems. When the results of the UVL studies were pooled, statistically significant reduction ins C. difficile infection (CDI) (pRR, 0.64; 95% confidence interval [CI], 0.49-0.84) and VRE infection rates (pRR, 0.42; 95% CI, 0.28-0.65) were observed. No differences were found in rates of MRSA or gram-negative multidrug-resistant pathogens. CONCLUSIONS Ultraviolet light no-touch disinfection technology may be effective in preventing CDI and VRE infection. Infect Control Hosp Epidemiol 2018;39:20-31.