Introduction: Maintaining oral health care of patients with an endotracheal tube is one of the most important responsibility of nurses. This study was conducted to compare the effect of two mouthwashes (Echinacea and chlorhexidine) on the oral health of patients in intensive care units. Methods: This is a randomized clinical trial that 70 unconscious patients with an oral endotracheal tube, the age of 18-65 years were enrolled with simple sampling and randomly divided into experimental (Echinacea) and control (chlorhexidine) groups. Before (first day) and after the intervention (fourth day), data was collected using an oral health checklist. For data analysis, SPSS-16 software, Chi-square, Fisher exact test, student t test, and Friedman test were used. Results: There was no significant difference between intervention and control groups in terms of demographic characteristics, oral health, and other characteristics (P=0.4). Oral health between intervention and control groups showed no significant differences after 4 days (P=0.27). Before and after the study, oral health of intervention group (Echinacea), have been improved and the difference was significant (P<0.0001). In addition, oral health of control group (chlorhexidine), have been improved and the difference was significant (P<0.0001). In other words, the effect of Echinacea on oral health is as same as chlorhexidine. Conclusion: Oral health of patients in intervention (Echinacea) and control (chlorhexidine) groups wereimproved equally. Due to the advantages of herbal medicine, the Echinacea can be considered as an alternative to chlorhexidine.