Background: Glaucoma is the leading cause of irreversible blindness in the USA. Glaucomatous vision loss is preventable with proper eye care, including appointment adherence. Therefore, interventions that improve appointment adherence can reduce the number of patients with more severe glaucoma. Objectives: The primary study aim was to determine the efficacy and cost-effectiveness of a multifaceted personal reminder intervention, which included a customized letter and personal telephone outreach, in improving appointment adherence of patients with glaucoma. A secondary study aim was to identify patient characteristics that were associated with non-adherence. Methods: This prospective, randomized, controlled study included a cost-effectiveness analysis completed using a decision analytic model. The subjects included 256 patients with glaucoma. Study measures included appointment adherence and incremental cost effectiveness ratios. Results: Patients in the intervention group were more likely to adhere to appointments (82.31 vs. 69.05 %; RR 1.23; 95 % CI 1.04–1.37, p < 0.012) than patients in the usual care group. Patients in the intervention group were 23 % more likely to adhere to appointments (RR 1.23; 95 % CI 1.08–1.41, p < 0.0021) than patients in the usual care group, when adjusting for age, secondary insurance, primary open angle glaucoma diagnosis, number of previous visits at Wills Eye Hospital, and follow-up recommendation using Poisson regression. Per-patient cost of the program was US$11.32, and cost per follow-up attended within the adherence window was US$73.56. Conclusions: A low cost reminder intervention consisting of a personalized letter and telephone outreach significantly improved appointment adherence of patients with glaucoma.