Abstract Background Information on HRQOL can enhance patient diagnosis and management but it is rarely available in routine clinical practice. This mixed-method study evaluated the feasibility and acceptability of the electronic EQ-5D-5L measurement of HRQOL in patients with chronic musculoskeletal problems in primary care. Methods In three primary care clinics, 665 patients with musculoskeletal problems completed the electronic EQ-5D-5L and Visual Analogue Scale (e-EQ-5D-5L/VAS), and a questionnaire on socio-demographics, perceived ease of use (PEOU), and perceived usefulness (PU) at baseline and two follow-ups. Patient completion and response rates, and time to complete the e-EQ-5D-5L/VAS were measured. During the same consultations, 49 doctors reviewed the e-EQ-5D-5L/VAS reports and completed a clinician questionnaire on PEOU, PU, and time spent to address each report. Individual interviews along with focus group discussions were conducted on patients, doctors, and research assistants for further exploration. Results Mean completion time reduced from baseline to first and second follow-up (120.66, 83.99, and 105.22 s, respectively). Completion and response rates were high at each follow-up visit (> 99.8% and > 91.11%, respectively). Doctors needed less than 2 min to read the report but felt the time required to address the report was a significant barrier. Some patients had difficulties using e-platforms, in understanding or answering questions; but, PEOU improved with time (p < 0.001). Most patients found the e-platforms useful (> 85.3%). Clinicians agreed a great majority of the reports were easy to use (76.0–85.1%) and useful (69.2–72.0%), particularly aiding with a holistic view of the patient's musculoskeletal problem. Conclusion The e-EQ-5D-5L/VAS is a feasible and acceptable measurement of HRQOL of patients with chronic musculoskeletal problems in routine primary care in Hong Kong which can assist real-time management decisions. Trial registration: NCT03609762.