Background: Sedation improves comfort during invasive mechanical ventilation (MV) in critically ill patients, but its deleterious effects are increasingly being recognized. We aimed to describe the relationship between patient-ventilator, sedation levels and administered molecules (sedatives and/or opioids). Methods: Prospective multicentre observational trial of critically ill adults mechanically ventilated >24 hours. Level of sedation and sedative and opioid doses were recorded. Asynchronies were continuously classified in all patients with Better Care™ software as: ineffective inspiratory efforts during expiration (IEE), double cycling (DC), and asynchrony index (AI). The relationship between asynchronies, sedation level, sedative and opioid doses were analysed with linear mixed-effects models. Findings: Between October 2011 and January 2013, 79 enrolled patients accounted for 579 days of ventilatory support (14,166,469 breaths). Overall AI, IEE and DC were similar in sedatives-only, opioids-only, or sedatives-plus-opioids recipients. All asynchronies were higher in subjects receiving no drugs. Sedative doses were associated with sedation level and with reduced DC (p