Objective: To evaluate the efficacy and safety of intrathecal morphine (ITM) for postoperative pain control in patients with renal cell carcinoma undergoing open nephrectomy. Methods: Forty-five patients scheduled for open nephrectomy were randomised to receive 300 µg ITM and intravenous patient-controlled analgesia (IV-PCA) (n = 22) or IV-PCA alone (n = 23) for postoperative analgesia. The numeric pain score (NPS), postoperative IV-PCA requirements and opioid-related complications including nausea, vomiting, dizziness, headache, and pruritus were compared between groups. Results: NPS was significantly lower in the ITM group up to 24 h postoperatively. Upon coughing, NPS at 24 h postoperatively was 50 (interquartile range (IQR) 30–60) in the ITM group and 60 (45–70) in the IV-PCA group. Cumulative morphine consumption at 72 h postoperatively was significantly lower in the ITM group compared with the IV-PCA group (20 (9–33) mg vs. 31 (21–49) mg, respectively). Opioid-related complications were similar in both groups with the exception of pruritus (ITM, 77% vs. IV-PCA, 26%). Conclusions: ITM was associated with greater analgesia without serious complications in patients undergoing open nephrectomy.