To investigate whether reflexology has an effect on the physiological signs of anxiety and level of sedation in patients receiving mechanically ventilated support, a single blinded, randomized controlled design with repeated measures was used in the intensive care unit of a university hospital in Turkey. Patients (n = 60) aged between 18 and 70 years and were hospitalized in the intensive care unit and receiving mechanically ventilated support. Participants were randomized to a control group or an intervention group. The latter received 30 minutes of reflexology therapy on their feet, hands, and ears for 5 days. Subjects had vital signs taken immediately before the intervention and at the 10th, 20th, and 30th minutes of the intervention. In the collection of the data, “American Association of Critical-Care Nurses Sedation Assessment Scale” was used. The reflexology therapy group had a significantly lower heart rate, systolic blood pressure, diastolic blood pressure, and respiratory rate than the control group. A statistically significant difference was found between the averages of the scores that the patients included in the experimental and control groups received from the agitation, anxiety, sleep, and patient-ventilator synchrony subscales of the American Association of Critical-Care Nurses Sedation Assessment Scale. Reflexology can serve as an effective method of decreasing the physiological signs of anxiety and the required level of sedation in patients receiving mechanically ventilated support. Nurses who have appropriate training and certification may include reflexology in routine care to reduce the physiological signs of anxiety of patients receiving mechanical ventilation.