To assess the psychometric properties of the behavioral indicators of pain scale (ESCID) when applied to a wide range of medical and surgical critical patients. A multicentre, prospective observational study was designed to validate a scale measuring instrument. Twenty Intensive Care Units of 14 hospitals belonging to the Spanish National Health System. A total of 286 mechanically ventilated, unable to self-report critically ill medical and surgical adult patients. Pain levels were measured by two independent evaluators simultaneously, using two scales: ESCID and the behavioral pain scale (BPS). Pain was observed before, during, and after two painful procedures (turning, tracheal suctioning) and one non-painful procedure. ESCID reliability was measured on the basis of internal consistency using the Cronbach-α coefficient. Inter-rater and intra-rater agreement were measured. The Spearman correlation coefficient was used to assess the correlation between ESCID and BPS. A total of 4386 observations were made in 286 patients (62% medical and 38% surgical). High correlation was found between ESCID and BPS (r=0.94-0.99; p<0.001), together with high intra-rater and inter-rater concordance. ESCID was internally reliable, with a Cronbach-α value of 0.85 (95%CI 0.81-0.88). Cronbach-α coefficients for ESCID domains were high: facial expression 0.87 (95%CI 0.84-0.89), calmness 0.84 (95%CI 0.81-0.87), muscle tone 0.80 (95%CI 0.75-0.84), compliance with mechanical ventilation 0.70 (95%CI 0.63-0.75) and consolability 0.85 (95%CI 0.81-0.88). ESCID is valid and reliable for measuring pain in mechanically ventilated unable to self-report medical and surgical critical care patients. CLINICALTRIALS.GOV: NCT01744717.