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It is a common clinical observation that postoperative pain may be resistant to morphine. The analgesic potentials of ketamine have also been well documented. In this study, we evaluated the effects of postoperative coadministration of small doses of ketamine and morphine on pain intensity, Spo2, and subjectively rated variables in surgical patients who underwent standardized general anesthesia and complained of pain (≥6 of 10 on a visual analog scale [VAS]) despite >0.1 mg/kg of IV morphine administration within 30 min. Patients randomly received up to three boluses of 30 μg/kg of morphine plus saline (MS;n = 114) or 15 μg/kg of morphine plus 250 μg/kg of ketamine (MK;n = 131) within 10 min in a double-blinded manner. The MS group’s pain VAS scores were 5.5 ± 1.18 and 3.8 ± 0.9 after 10 and 120 min, respectively, after 2.52 ± 0.56 injections, versus the MK group’s VAS scores of 2.94 ± 1.28 and 1.47 ± 0.65, respectively (P < 0.001), after 1.35 ± 0.56 injections (P < 0.001). The 10-min level of wakefulness (1–10 VAS) in the MS group was significantly (P < 0.001) less (6.1 ± 1.5) than the MK group’s (8.37 ± 1.19). Spo2 decreased by 0.26% in the MS group but increased by 1.71% in the MK patients at the 10-min time point (P < 0.001). Thirty MS versus nine MK patients (P < 0.001) experienced nausea/vomiting; nine MK patients sustained a 2-min light-headed sensation, and one patient had a weird dream after the second drug injection.