BACKGROUND: Data are scarce regarding the usefulness of a pharmaceutical therapy-related quality of life measure including the Patient-Reported Outcomes Measure of Pharmaceutical Therapy for Quality of Life (PROMPT-QoL), for providing pharmaceutical care. AIM: To evaluate the impact of the PROMPT-QoL on identifying drug-related problems (DRPs), physicians' acceptance of pharmacist's recommendations on the DRP resolution, and clinical and quality of life outcomes. METHOD: A single-blind randomized controlled trial was conducted at a tertiary public hospital in Thailand from October 2019 to May 2020. A total of 286 outpatients with chronic diseases were randomly allocated into the control group (provided with pharmaceutical care only) (N = 146) and the intervention group (provided with pharmaceutical care together with use of the PROMPT-QoL) (N = 140). RESULTS: A significantly higher mean number of DRPs could be identified in the intervention group than in the control group (p < 0.001). Moreover, there was a significantly higher proportion of physicians' acceptance of pharmacist's recommendations on the DRP resolution in the intervention than in the control group (p = 0.019). Regarding the clinical outcome, a significantly higher proportion of the DRP resolution was found in the intervention group than in the control group (p = 0.002). For quality of life outcomes, the intervention group yielded a significantly higher mean difference between posttest and pretest on the Medicine and Disease Information domain score of the PROMPT-QoL (p = 0.029) and the EuroQoL-Visual Analog Scale score (p = 0.031) than the control group. CONCLUSION: This study revealed that the application of the PROMPT-QoL together with pharmaceutical care favorably influenced identification of DRPs, physicians' acceptances, and clinical outcomes. Trial registration TCTR20201208005 on December 5, 2020.