OBJECTIVES: Treatment satisfaction with drug therapies is an important patient-reported-outcome (PRO) that may help clinicians to better impact in patient healthcare. The Treatment Satisfaction with Medicines (SATMED-Q) questionnaire has shown appropriate psychometric properties for exploring patient’s satisfaction with medicines under routine medical practice in chronic health conditions. The Minimally Important Difference (MID) of the instrument is still unknown. The goal of this research was to determine the MID values of the SATMED-Q questionnaire for the total score and domains. METHODS: The sample of patients (457, mean age 59 years, 53% male) used for testing psychometric properties was also used to assess MID values. Item #14 of the TSQM scale was used as an anchor reference, since it explores directly the satisfaction with medicines in a seven points ordinal response (from extremely satisfied to extremely dissatisfied). Patients were classified into four categories according with responses in  this item; extremely satisfied/dissatisfied, very satisfied/dissatisfied, satisfied/dissatisfied, nor satisfied/nor dissatisfied and comparisons were carried out for the overall score and each domain of the SATMED-Q  using standardized scores. The mean differences in overall score (and domains) between the neutral category and the satisfied/dissatisfied category were considered the values of MID. Effect sizes (ES) were also computed. RESULTS: MID for total scoring was 13.4 (ES=0.91), while the value for domains ranged from 10.3 (medical care domain, ES=0.43) to 20.6 (impact of daily living, ES= 0.85). Mean score differences in overall scale and domains were significant between change in satisfaction categories with respect item#14 with F values ranging from 9.7 to 74.1 (p<0.001 in all cases). CONCLUSIONS: The SATMED-Q demonstrated to be responsive to different levels of patient´s satisfaction with therapy in chronically ill subjects. Attained MID was 13.4 pts for the overall normalized scoring scale and between 10.3 and 20.6 pts for domains.