ABSTRACT Purpose To identify prevalence of and risk factors for loss to follow up (LTFU) among a national cohort of patients with primary open-angle glaucoma (POAG). Methods This retrospective cohort study analyzed data from the IRIS® Registry (Intelligent Research in Sight) database from 2014 through 2019 to assess LTFU among adult patients with POAG. POAG patients with at least one clinical encounter in 2014 were included. LTFU was defined as exceeding one year without a clinical encounter during the study period. Results Among 553,663 glaucoma patients, 277,019 (50%) became LTFU, of whom 184,548 (67%) never returned to care and 92,471 (33%) re-established follow-up after a lapse. Risk of LTFU was greatest among those younger than 60 years (RR = 1.38; 95% CI: 1.36–1.39) or older than 80 years (RR = 1.39; 95% CI: 1.38–1.40) compared to those in their 60s. Compared to White race, risk for LTFU was highest among Native Hawaiian/Pacific Islander (RR = 1.24; 95% CI: 1.17–1.31), Hispanic ethnicity (RR = 1.19; 95% CI: 1.18–1.20), and Black race (RR = 1.10; 95% CI: 1.09–1.11). Medicare insurance was associated with lower risk of LTFU (RR = 0.79; 95% CI: 0.78–0.79), whereas unknown/missing/no insurance was associated with greater risk (RR = 1.33; 95% CI: 1.32–1.34), compared to private insurance. Compared to mild-stage POAG, risk of LTFU was higher for moderate-stage (RR = 1.10; 95% CI: 1.08–1.13) and severe-stage disease (RR = 1.35; 95% CI: 1.32–1.38). Conclusion We found a 50% prevalence of LTFU among POAG patients in the IRIS Registry over a 6-year study period, with greater risk among minority groups and those with more advanced disease.