Metformin was recently found to increase fetal hemoglobin, which is protective in sickle cell disease (SCD). We tested the hypothesis that, among adults with SCD and diabetes mellitus (DM), metformin use is associated with fewer adverse SCD clinical outcomes and lower health care utilization. This is a retrospective cohort study using the MarketScan Medicaid claims database for 2006 to 2016, comparing metformin users and nonusers. Patients on hydroxyurea, insulin, or iron chelation were excluded. Main outcomes included annual rates of all-cause inpatient encounters, all-cause emergency department (ED) encounters, inpatient and ED encounters with SCD codes, vaso-occlusive episodes (VOEs), strokes, acute chest syndrome (ACS), avascular necrosis (AVN), and gallstones. Of 457 adults (median age [interquartile range], 43 years [33-52 years]; 72% female), 142 (31%) were treated with metformin. Adjusted for age, sex, and Charlson Comorbidity Index, metformin users had significantly lower rate ratios of all-cause inpatient encounters (0.68; 95% confidence interval [CI], 0.52-0.88; P < .01), inpatient encounters with SCD codes (0.45; 95% CI, 0.30-0.66; P < .01), ED encounters with SCD codes (0.34; 95% CI, 0.21-0.54; P < .01), VOE (0.22; 95% CI, 0.12-0.41; P < .01), ACS (0.17; 95% CI, 0.05-0.60; P = .01), and AVN (0.30; 95% CI, 0.11-0.87; P = .03). A subgroup analysis of 54 enrollees preinitiation and postinitiation of metformin did not indicate significant changes in rates of clinical events. Metformin was associated with significantly fewer inpatient and ED SCD encounters in adults with SCD and DM; however, confounding of underlying SCD severity cannot be excluded.