BackgroundThe Generic Adherence for Chronic Diseases Profile is a French generic scale (GACID-P) developed to measure adherence in several disease areas such as cardiology, rheumatology, diabetes, cancer and infectiology.MethodWe aimed to study the measurement invariance of the Generic Adherence for Chronic Diseases Profile by an item response model, optimize the new instrument version from item response model and qualitative content analyses results, and validate the instrument. The metric properties of the optimized version were studied according to classical test theory and item response model analysis.ResultsA sample of 397 patients consulting at two French hospitals (in diabetes, cardiology, rheumatology, cancerology and infectiology) and in four private practices was recruited; 314 (79%) patients also completed the questionnaire 15 days later. Factor analyses revealed four dimensions: “Forgetting to take medication”, “Intention to comply with treatment”, “Limitation of risk-related consumer habits” and “Healthy lifestyle”. The item response model and content analyses optimized these four dimensions, regrouping 32 items in four dimensions of 25 items, including one item conditioned on tobacco use. The psychometric properties and scale calibration were satisfactory. One score per dimension was calculated as the sum of the items for the dimensions “Forgetting to take medication” and “Intention to comply with treatment” and as a weighted score according to the item response model analysis for the two other dimensions because of differential item functioning found for two items.ConclusionFour adherence profile scores were obtained. The instrument validity was documented by a theoretical approach and content analysis. The Generic Adherence for Chronic Diseases Profile is now available for research targeting adherence in a broad perspective.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12955-023-02130-0.