The aim of this study was to compare the clinical performance of a self-etching primer (SEP) with a conventional two-step etch and primer [conventional method (CM)]. The chair time required for bonding was also evaluated. Thirty-seven patients (14 males and 23 females) with a mean age of 16 years 5 months were included in the study. Six hundred and seventy-two brackets were bonded by one operator using a split-mouth design, with either SEP (Transbond Plus) or CM (Transbond XT). Bracket failure rates were estimated with respect to bonding procedure, dental arch, type of tooth (incisor, canine, and premolar), and gender. The results were evaluated using the chi-square test. The survival rate of the brackets was estimated with Kaplan-Meier analysis. Bracket survival distributions with respect to bonding procedure, dental arch, type of tooth, and patient gender were compared with a log-rank test. Bond failure interface was determined with the adhesive remnant index (ARI). The failure rates were 0.6 per cent for both bonding procedures. The failure and survival rates did not show significant differences between the bonding procedures, upper and lower dental arches, or gender. However, premolar brackets displayed a higher bond failure rate and a lower survival rate than incisor and canine brackets (P < 0.05). The mean bracket bonding time per tooth with SEP was significantly shorter than with CM (P < 0.001). No significant difference was observed for the ARI scores (P > 0.05). The results of this in vivo, randomized, cross-mouth clinical trial demonstrated a high survival rate with Transbond Plus. This finding indicates that SEP can be effectively used for bonding of orthodontic brackets.