Abstract Fentanyl pectin nasal spray (FPNS) is being developed to improve analgesic onset, treatment efficacy, and satisfaction/acceptability in treating breakthrough cancer pain (BTCP). Patients (n = 114) were entered into a randomized, placebo-controlled, double-blind, multicenter study. Patients who successfully titrated (n = 83) entered a double-blind phase; 10 episodes of BTCP were treated with the effective dose (7) or placebo (3). Pain intensity (11-point scale) and pain relief (5-point scale) were assessed between 5 and 60 minutes. Use of rescue medications was recorded, and acceptability assessments were conducted 30 and 60 minutes post dose. Only 6% of patients failed to titrate to an effective dose of FPNS due to lack of efficacy and 5% due to adverse events. A total of 91% of randomized patients completed the study. Episode analysis (FPNS, n = 459; placebo, n = 200) revealed that compared with placebo, 33% of FPNS episodes showed an onset of improvement in pain intensity at 5 minutes (P < 0.05); 33% of episodes by 10 minutes had clinically meaningful pain relief (> or = 2 point decrease in pain intensity; P < 0.0001). Satisfaction with the convenience and ease of use of FPNS was reported by 70% and 68% of patients, respectively; 87% of patients elected to continue treatment post study. FPNS provided rapid analgesia in BTCP and was well accepted by patients.