The objective of this study was to evaluate whether dispensing prescriptions in the ED affects patient compliance and return visits to the hospital. Seventy-four patients who were deemed suitable candidates for outpatient therapy with a macrolide antibiotic were identified and prospectively randomized to receive either an entire course of azithromycin from the ED or a prescription for azithromycin to be filled at a local pharmacy free of charge. Pharmacy records and telephone interview were used to measure compliance with patients. Significantly fewer patients filled their prescription in the pharmacy group (74.2%) compared with the ED group, in which all patients received their medication. However, there was no difference in the self-reported compliance of completing the entire course of antibiotics between patients in the ED group (94.3%) and in the pharmacy group (96.8%). There was no significant difference between groups in return ED visits or hospital admissions. We conclude that delivery of prescriptions in the ED significantly increases the likelihood that the patient will obtain the medication prescribed. Whether the patients actually take the medication as directed is unknown. Patient's self-report did not accurately reflect true compliance and more objective means for measuring compliance is warranted.