Abstract Background Venous cannulation is widely used in healthcare systems, and for many patients, it is painful and distressing. We hypothesized that the rapid onset of cryospray use would reduce pain from venous cannulation compared to the use of a placebo spray. Methods The trial was a prospective randomized placebo-controlled trial including 130 adult patients scheduled for elective surgery. Patients were randomized to receive either cryospray or placebo before venous cannulation. The primary outcome was patient-reported pain from vein puncture. Results There were no differences in the baseline variables between the two groups with respect to age, sex, height, weight or ASA class. Patients in the cryospray group indicated more pain or discomfort with the application of the spray (0 (0-2.5)) than with the application of the placebo spray (0 (0–0)) (P