The aim of this study was to evaluate the use of fluoride varnish as a prophylaxis method with self etching primer (SEP) and its comparison with pumice before orthodontic bonding. Thirty seven orthodontic patients participated in a prospective clinical trial. A split mouth technique was used in each patient, one quadrant was assigned to fluoride varnish and the contralateral quadrant to pumice prophylaxis. A total of 684 teeth were bonded with SEP (Transbond plus; 3M Unitek) and monitored for 6 months for bond failures. A total of 42 (6.1%) failures were recorded, 9 (2.6%) in the pumice group and 33 (9.6%) in the fluoride varnish group. Chi-square analysis was used to compare the number of bracket failures between the pumice and fluoride varnish groups and the number of patients in each group experiencing at least one bond failure. Statistically significant differences were found both in total number of bond failures (P < 0.001) and in the number of patients with bond failures (P < 0.05) between both groups. A significantly lower and clinically acceptable bond failure rate was observed with Transbond Plus self etching primer after pumice prophylaxis.