Summary Background Intrathecal diamorphine is believed to provide postoperative analgesia but is associated with adverse effects such as nausea and vomiting. There is little evidence of synthesis regarding intrathecal diamorphine in the contemporary literature. We performed a systematic review, meta‐analysis with meta‐regression and trial sequential analysis to determine the magnitude of intrathecal diamorphine efficacy and safety. Methods We systematically searched the literature for trials comparing intrathecal diamorphine with a control group in patients undergoing all types of surgery. The primary efficacy and safety outcomes were intravenous morphine consumption and incidence of postoperative nausea and vomiting at 24 h following surgery, respectively. Results Twelve trials were identified, which included data for 712 patients. Intrathecal doses of diamorphine ranged from 100 μg to 2500 μg. Intravenous morphine consumption at 24 h postoperatively was significantly reduced in the intrathecal diamorphine group, with a mean difference (95%CI) of ‐8 mg (‐11 to ‐6), I 2 = 93%, p < 0.001. There was a significant difference between three intrathecal diamorphine dosing subgroups but without correlation: mean differences (95%CI) ‐1 mg (‐3–0), ‐26 mg (‐40 to ‐11) and ‐6 mg (‐15–4) in patients receiving doses of 0–200 μg, 201–400 μg and > 400 μg, respectively (p = 0.003). Intrathecal diamorphine increased postoperative nausea and vomiting with a risk ratio (95%CI) of 1.37 (1.19–1.58), I 2 = 7%, p < 0.001. There were no differences in postoperative nausea and vomiting between the three intrathecal diamorphine dosing subgroups. There was no correlation observed with meta‐regression of the primary efficacy and safety outcomes. The quality of evidence for all outcomes was very low. Conclusion There is very low level of evidence that intrathecal diamorphine provides effective analgesia after surgery, while increasing postoperative nausea and vomiting with doses > 200 μg.