Background: The treatment of esophageal achalasia is still controversial: current therapies are palliative and aim to relieve dysphagia by disrupting or relaxing the lower esophageal sphincter muscle fibers with botulinum toxin. The aim of this study was to compare the clinical and economic results of two such treatments: laparoscopic myotomy and botulinum toxin injection. Methods: A total of 37 patients with esophageal achalasia were randomly assigned to receive laparoscopic myotomy (20) or two Botox injections 1 month apart (17). All patients were treated at the same hospital and were part of a larger multicenter study. Symptom score, lower esophageal sphincter pressure, and esophageal diameter at barium swallow were compared. The economic analysis was performed considering only the direct costs (cost per treatment and cost effectiveness, i.e., cost per patient healed). Results: Mortality and morbidity were nil in both groups. The actuarial probability of being asymptomatic at 2 years was 90% for surgery and 34% for Botox (p < 0.05). The initial cost was lower for Botox (€1,245) than for surgery (€3,555), but when cost effectiveness at 2 years was considered, this difference nearly disappeared: Botox €3,364, surgery €3,950. Conclusion: Botox is still the least costly treatment, but the minimal difference in the longer term does not justify its use, given that surgery is a risk-free, definitive treatment.