- Objective: Sedation is frequently required in critically ill, mechanically ventilated patients. Sedation and analgesia requirements may vary substantially among patients. This study examined whether psychological factors predict amount of sedation requirements beyond the effects of other biomedical parameters. Methods: This study used a prospective correlative design in an eight-bed medical intensive care unit at a tertiary university hospital. Fifty-five adult patients requiring mechanical ventilation were included. We evaluated by questionnaires three psychological factors of patients—hostility, anxiety and desire for control (DC)—as completed by patients’ relatives at entry to the intensive care unit. Daily doses of sedatives required were monitored. The primary outcome measurement was midazolam dose expressed in mg/kg/h. Results: There was a statistically significant correlation between psychological factors and midazolam dose (mg/kg/h): r values = 0.40 for anxiety, 0.43 for hostility, and 0.46 for DC. Age and pulmonary edema were inversely related to midazolam requirements, whereas smoking, chronic obstructive pulmonary disease, fentanyl dose, and therapeutic intervention scoring system were positively correlated with midazolam doses. In a multiple regression, DC accounted for an additional and significant 5.4% of the variance in midazolam after controlling statistically for the effects of the significant background and biomedical predictors. In the final regression equation, DC and fentanyl were the only significant factors associated with higher sedation requirement. Conclusion: Premorbid psychological profile independently predicts sedation requirement in critically ill, mechanically ventilated patients. Early identification of such a profile may help in sedation management and patient care. The possible mechanisms and clinical implications are discussed. MV = mechanical ventilation; ICU = intensive care unit; DC = desire for control; APACHE II = Acute Physiology Age Chronic Health Evaluation II; TISS = Therapeutic Intervention Scoring System; COPD = chronic obstructive pulmonary disease.