Background: Automated phone appointment reminders have improved adherence with follow-up appointments in a variety of hospital settings, but have mixed results in patients discharged from the emergency department (ED). Increasing adherence to follow-up care has been a priority in the ED to improve patient outcomes and reduce unnecessary future visits. Methods: We conducted a prospective randomized open, blinded end-point (PROBE) trial of 278 adult patients discharged from the ED and referred to a provider for follow-up care. Participants in the intervention arm received a self-scheduling text or phone message that automatically connected them to their referral provider to schedule a follow-up appointment and sent them appointment reminders. Those in the control arm received standard-of-care written instructions to contact listed referral providers. The primary outcome was time to appointment. The secondary outcome was time to return visit to the ED. Results: The automated reminders increased the cumulative incidence of keeping the referral appointment after ED discharge (p < 0.001, Gray's test). Of participants randomized to the automated phone intervention, 49.3% (n = 74) kept their follow-up appointment versus 23.4% (n = 30) in the control arm, with a hazard ratio (HR) and 95% confidence interval (CI) over the duration of the study period of 2.4 (1.6 to 3.7; p < 0.001). In a sensitivity analysis using 30 days of follow-up data, 42.0% (n = 63) of participants randomized to the phone intervention kept their follow-up versus 21.1% (n = 27) in the control arm, with a HR (95% CI) of 2.2 (1.4 to 3.5; p < 0.001). There was no difference in ED revisits between the intervention and control group within 120 days postdischarge. Conclusions: An automated self-scheduling phone system significantly improved follow-up adherence after ED discharge, but did not decrease ED revisits.