Squaric acid dibutyl ester (SADBE) is a commonly used treatment for verruca vulgaris of childhood. Few studies, however, have examined the role of SADBE in combination with other topical therapies for warts. We sought to determine if trichloroacetic acid 50% (TCA) and/or cantharidin 0.7% improve therapeutic response to SADBE. A retrospective chart review of 74 patients who were treated for warts at a pediatric dermatology practice in 2010 was performed. Cox regression analysis was used to identify determinants of 100% response to SADBE and found that number of warts was most important (P=0.002). Trichloroacetic acid + SADBE resulted in 100% clearance of warts in all subjects with the shortest time-to-clearance (hazard ratio [HR]: 2.45, 95% confidence interval [CI]: 1.14-5.25, P=0.02). In contrast, addition of cantharidin did not improve response to SADBE (HR: 1.13, 95% CI: 0.60-2.13, P=0.59) or TCA + SADBE (HR: 1.16, 95% CI: 0.65-2.07, P=0.61). These results suggest that combination treatment with TCA 50% and SADBE significantly improves the consistency and speed of SADBE-induced clearance of warts.