BACKGROUND AND OBJECTIVES: This study aimed at comparing epidural thoracic S(+) ketamine and morphine, both associated to ropivacaine, for mastectomy procedures. METHODS: This is a prospective study with 26 patients aged between 18 and 70 years, submitted to mastectomy, who were divided into two equal groups. Group M (morphine) patients have received 12 mL of 0.75% ropivacaine associated to 2 mg preservative-free morphine; Group K (ketamine) patients have received 12 mL of 0.75% ropivacaine associated to 50 mg of preservative-free S(+) ketamine. We have evaluated hemodynamic parameters, need for vasopressors, drugs for sedation, pain visual analog scale in the first 24 hours, analgesic and antiemetic consumption, and incidence of nausea and vomiting. RESULTS: There has been no statistical difference between groups in demographics, systolic and diastolic blood pressure, amount of local anesthetics or need for vasopressors. The ketamine group has demanded more midazolam to control sedation (p = 0.0005). This group had lower pain scores at post-anesthetic care unit discharge (p = 0.0018), 12 hours after procedure (p = 0.0001) and 24 hours later (p = 0.0094). The Morphine Group had higher pain scores at post-anesthetic care unit, 12 and 24 postoperative hours, and has demanded more postoperative analgesics (dipirone, p = 0.0009) and antiemetics (metoclopramide, p = 0.0032). CONCLUSION: It has been observed that S(+) ketamine in the evaluated dose was hemodynamically safe and effective, with better performance to control postoperative pain, generating less analgesic consumption as well as lower incidence of nausea and vomiting.