Routine oral care with chlorhexidine may prevent lower respiratory tract infections in cardiac surgery patients but seems to be of limited benefit for non–cardiac surgery patients. Meta-analysis of double-blind investigations suggests that chlorhexidine’s capacity to prevent VAP and improve outcomes is questionable. Large randomized clinical trials powered to detect a 10% or greater difference in mortality rates are needed to definitively evaluate the safety and benefits of routine oral care with chlorhexidine. In addition, we suggest that future trials include acute respiratory distress syndrome as an outcome. While our findings are not conclusive, they are sufficiently concerning to prompt a reevaluation of policies and initiatives that encourage or compel hospitals to include chlorhexidine in routine oral care for non–cardiac surgery patients.