To quantify risks associated with drug utilization in the real world for the treatment of chronic pain (CP), an index called the Medication Quantification Scale (MQS) was developed in 1992 in the United States and last updated in 2003. This study aimed to update, adapt to the contemporary Canadian context, and validate a revised version of the MQS (the MQS-4.0). Step 1: An expert committee adapted the MQS to the Canadian clinical practice context. Step 2: An update of risk weights given to medication subclasses was achieved using a prescriber survey (weights were derived from median 0-10 scores given to each subclass). Step 3: Construct validity of the MQS-4.0 was assessed after applying risk weights to the medication use profile of persons living with CP covered by public drug insurance plan. Thirty-six medication subclasses were included in the MQS-4.0. A total of 207 prescribers (physicians, pharmacists, and nurse practitioners) participated in the perception survey; 10.63% identified as pain specialists. When risk weights were applied to prescription claims (n=9,122), the MQS-4.0 score was associated (p<.05) with the MQS-III score and variables associated with polypharmacy (e.g., Charlson Comorbidity Index, number of prescribers or healthcare visits). This study provides an updated index intended for adult populations based on prescribers' perceptions of the risk associated with CP medications that can be useful for clinical practice and research among persons living with CP in Canada. It will, however, be relevant to verify whether similar risk weights are obtained in future pain specialist surveys. PERSPECTIVE: The MQS-4.0 is an update of the Medication Quantification Scale used for quantifying the risk associated with the use of analgesics/co-analgesics. Adequate psychometrics properties were found.Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.