OBJECTIVES: To compare the efficacy of opioids in reducing breakthrough pain within 15 min after taking the medication, in patients with cancer. METHODS: Randomised controlled trials investigating the efficacy of opioids administered orally or intranasally were identified with a systematic literature search. The endpoint of interest was the reduction in pain intensity (pain intensity difference (PID)) recorded on a 0 – 10 numeric rating scale within 15 min after taking the medication. Outcomes of all trials were analysed simultaneously with a Bayesian mixed treatment comparison. RESULTS: In addition to one trial report on the use of intranasal fentanyl spray (INFS), four relevant studies were identified, allowing comparisons between INFS, oral transmucosal fentanyl citrate (OTFC), fentanyl buccal tablet (FBT), and morphine sulphate immediate release (MSIR). INFS was more efficacious than placebo: the relative treatment effect, PID at 10 min post dosing (PID10), was 1.28 (positive values indicate a reduction in pain), 95% Credibility Interval (CrI): 0.91;1.65. OTFC and FBT at 15 min were also more efficacious than placebo: the relative treatment effect, PID15 (mean ± 95%CrI), was 0.60 (0.11;1.09) for OTFC and 0.51 (0.29;0.73) for FBT. MSIR displayed similar efficacy to placebo: PID15 0.18 (-0.50;0.86). INFS provided a greater pain reduction after 10 min than the other interventions after 15 min. The relative treatment effects of INFS (PID10) versus other treatments (PID15) were: 0.68 (0.06;1.30) versus OTFC, 0.77 (0.34;1.20) versus FBT and 1.10 (0.32;1.87) versus MSIR, corresponding to a probability of 98% or more of INFS being the most efficacious treatment.   CONCLUSIONS: The current study demonstrated that in the treatment of breakthrough pain in patients with cancer (i) MSIR has similar efficacy to placebo 15 min after dosing and (ii) INFS is the most efficacious treatment for reducing breakthrough pain within 15 min after dosing compared with OTFC, FBT and MSIR.