OBJECTIVES: Existing measures of opioid-induced constipation (OIC) symptoms have not been developed in accordance with FDA’s 2009 Guidance for Patient-Reported Outcome (PRO) Measures.  The OIC Rating Scale (ORS) was developed based on literature and comprehensive qualitative research.  This study aimed to: 1) validate a conceptual framework of two domains; 2) determine the optimal scoring system; 3) examine item- and scale-level psychometrics; and 4) establish domain responder definitions (RD). METHODS: ORS was administered to 215 US adults with OIC in a Phase II study.  Confirmatory factor analysis (CFA) was used to test the fit of the previously developed conceptual framework.  The evaluation analyzed data from the 2-week baseline period and the 5-week treatment period.  Item response theory (IRT) was used to determine an optimal scoring approach, followed by classical psychometrics including item- and scale-level reliability, and convergent validity.  Distribution- and anchor-based approaches were used to determine the RD for each domain based on week 5 change from baseline.    RESULTS: Based on descriptive statistics, item-level correlations, and CFA results (confirmatory fit index/non-normed fit index > 0.96, standardized root mean residual <0.04), a two-domain structure of the ORS was validated and carried forward in tests of reliability (αs > 0.85, test-retest ICCs > 0.60) and validity analyses (convergent rs 0.37-0.55), and to establish score interpretation.  IRT results provided no compelling evidence requiring special item weights rather than a simple raw sum-score per domain.  The two-item bowel movement symptom (BMS) domain RD = 2 and six-item gastrointestinal-related symptom (GRS) domain RD = 4. CONCLUSIONS: The ORS instrument demonstrated strong psychometric characteristics using analyses following the current FDA guidance for PRO measures.  The two domains explained the correlations among the bowel movement and gastrointestinal-related symptoms in OIC.  These results support further use of this instrument in studies of potential treatments for OIC.