Introduction The FreeStyle Libre (FSL) is a flash glucose monitoring (FGM) system. The Flash Monitor Register in the Netherlands (FLARE-NL-4) study previously demonstrated the positive effects of FSL-FGM use during 1 year on glycemic control, quality of life and disease burden among persons with diabetes mellitus (DM). The present follow-up study assesses the effects of FSL-FGM after 2 years. Research design and methods Patients included in the FLARE-NL-4 study who continued FSL-FGM during the 1-year study period were invited to participate (n=687). Data were collected using questionnaires (the 12-Item Short Form Health Survey version 2 (SF-12v2) and the EuroQol 5-Dimension 3-Level (EQ-5D-3L) for quality of life), including self-reported hemoglobin A1c (HbA1c). Results A total of 342 patients agreed to participate: mean age 48.0 (±15.6) years, 52% men and 79.5% with type 1 DM. HbA1c decreased from 60.7 (95% CI 59.1 to 62.3) mmol/mol before use of FSL-FGM to 57.3 (95% CI 55.8 to 58.8) mmol/mol after 1 year and 57.8 (95% CI 56.0 to 59.5) mmol/mol after 2 years. At the end of the 2-year follow-up period, 260 (76%) persons were still using the FSL-FGM and 82 (24%) had stopped. The main reason for stopping FSL-FGM was financial constraints (55%). Concerning the whole 2-year period, there was a significant decrease in HbA1c among persons who continued use of FSL-FGM (−3.5 mmol/mol, 95% CI −6.4 to –0.7), while HbA1c was unaltered compared with baseline among persons who stopped FSL-FGM (−2.4 mmol/mol, 95% CI −7.5 to 2.7): difference between groups 2.2 (95% CI −1.3 to 5.8) mmol/mol. After 2 years, persons who continued use of FSL-FGM had higher SF-12 mental component score and higher EQ-5D Dutch tariff score and felt less often anxious or depressed compared with persons who discontinued FSL-FGM. Conclusions Although the considerable number of non-responders limits generalizability, this study suggests that persons who continue to use FSL-FGM for 2 years may experience sustained improvement in glycemic control and quality of life.