This paper is aimed to develop the irritable bowel syndrome (IBS) scale of the system of Quality of Life Instruments for Chronic Diseases (QLICD-IBS) by the modular approach and validate it by both classical test theory and generalizability theory. The QLICD-IBS was developed based on programmed decision procedures with multiple nominal and focus group discussions, in-depth interview, and quantitative statistical procedures. One hundred twelve inpatients with IBS were used to provide the data measuring QOL three times before and after treatments. The psychometric properties of the scale were evaluated with respect to validity, reliability, and responsiveness employing correlation analysis, factor analyses, multi-trait scaling analysis, t tests and also G studies and D studies of generalizability theory analysis. Multi-trait scaling analysis, correlation, and factor analyses confirmed good construct validity and criterion-related validity when using SF-36 as a criterion. Test-retest reliability coefficients (Pearson r and intra-class correlation (ICC)) for the overall score and all domains were higher than 0.80; the internal consistency alpha for all domains at two measurements were higher than 0.70 except for the social domain (0.55 and 0.67, respectively). The overall score and scores for all domains/facets had statistically significant changes after treatments with moderate or higher effect size standardized response mean (SRM) ranging from 0.72 to 1.02 at domain levels. G coefficients and index of dependability (Dcurrency sign coefficients) confirmed the reliability of the scale further with more exact variance components. The QLICD-IBS has good validity, reliability, responsiveness, and some highlights and can be used as the quality of life instrument for patients with IBS.