Patients undergoing emergency procedures under general anesthesia have impaired gastric emptying and are at high risk for aspiration of gastric contents. Erythromycin has strong gastric prokinetic properties. To evaluate the efficacy of erythromycin lactobionate in gastric emptying in patients undergoing emergency surgery. The Erythro-Emerge trial was a single-center, randomized, double-blinded, placebo-controlled clinical trial in patients undergoing emergency surgery under general anesthesia at Geneva University Hospitals. We included 132 patients from March 25, 2009, through April 10, 2013, and all patients completed the study. Randomization was stratified for trauma and nontrauma procedures. The randomization code was opened on April 23, 2013, and analyses were performed through July 26, 2013. We performed an intention-to-treat analysis. Patients were randomized to intravenous erythromycin lactobionate, 3 mg/kg, or placebo 15 minutes before tracheal intubation. Patients were followed up for 24 hours. The primary outcome was a clear stomach, defined as less than 40 mL of liquids and no solids and identified through endoscopy immediately after intubation. The secondary outcome was the pH level of residual gastric content. A clear stomach was diagnosed in 42 of 66 patients (64%) receiving placebo compared with 53 of 66 patients (80%) receiving erythromycin (risk ratio, 1.26 [95% CI, 1.01-1.57]). In the population undergoing surgery for nontrauma, the association between receipt of erythromycin and having a clear stomach (adjusted odds ratio [95% CI]) was statistically significant (13.4 [1.49-120]; P = .02); in the population undergoing surgery for trauma, it was not (1.81 [0.64-5.16]; P = .26). Median (interquartile range) pH of the residual gastric liquid was 2 (1-4) in 36 patients receiving placebo and 6 (3-7) in 16 receiving erythromycin (P = .002). Patients receiving erythromycin had nausea (20 [30%] vs 4 [6%]) and stomach cramps (15 [23%] vs 2 [3%]) more often than those receiving placebo. One patient receiving erythromycin vomited before induction of anesthesia. In patients undergoing general anesthesia for emergency procedures, erythromycin administration increased the proportion with a clear stomach and decreased the acidity of residual gastric liquid. Erythromycin was particularly efficacious in the nontrauma population. Adverse effects were minor. Further large-scale studies are warranted to confirm the potential of erythromycin to reduce the incidence of bronchoaspiration in patients undergoing emergency surgery. ClinicalTrials.gov identifier: NCT00827216.