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Self-care refers to behaviors that individuals adopt to prevent or maintain the stability of an illness (self-care maintenance), to monitor signs and symptoms (self-care monitoring), and to respond to signs and symptoms of an illness exacerbation (self-care management). A generic measure of self-care, the Self-Care of Chronic Illness Inventory, based on the Theory of Self-Care of Chronic Illness, was developed for use in individuals with any number and type of chronic conditions. The current study investigated the measurement equivalence of the Self-Care of Chronic Illness Inventory in individuals from three different cultural groups. We were interested in determining if Italians, Swedes, and Americans interpret the measure in a conceptually similar way. This cross-sectional study enrolled 1629 patients, 784 recruited in Italy, 438 in Sweden and 407 in the United States. Self-care (self-care maintenance, self-care monitoring and self-care management) was measured with the Self-Care of Chronic Illness Inventory. A multi-group confirmatory factor analytic approach was used to assess the equivalence of the measures across the three countries. Configural, metric, scalar and strict invariance were tested through a series of nested models where increasingly stringent equality constraints were posited. Participants were mostly males (56.3%), older adults (69.8%) and had at least two chronic conditions. Results indicated that three out of four measurement equivalence levels were partially or totally supported in all three of the Self-Care of Chronic Illness Inventory scales. The partial scalar invariance level was reached for self-care maintenance [χ2(50) = 63.495, p = 0.095; RMSEA = 0.022, p = 0.999, 90% CI = 0.000 0.038; CFI = 0.981; TLI = 0.977; SRMR = 0.036], self-care monitoring [χ2(22) = 28.770, p = 0.095; RMSEA = 0.024, p = 0.978, 90% CI = 0.000 0.046; CFI = 0.996; TLI = 0.995; SRMR = 0.054], and self-care management [χ2(51) = 91.334, p = 0.001; RMSEA = 0.048, p = 0.576, 90% CI = 0.031 0.063; CFI = 0.949; TLI = 0.937; SRMR = 0.047] scales. These findings suggest that patients in the three countries used an identical cognitive framework or mental model when responding and used the 1–5 Likert response scale in an almost identical way, almost without bias. In spite of sociocultural differences, patients in these countries seem to share the same fundamental view of self-care. The results of the Self-Care of Chronic Illness Inventory will be comparable in these countries. [ABSTRACT FROM AUTHOR]