Plantar warts are one of the most common infectious skin disease caused by the human papillomavirus. In this study, cryotherapy with liquid nitrogen delivered by the physician, up to four treatments 2 weeks apart. Forty percent trichloroacetic acid (TCA) was applied to warts weekly up to four treatments. At the end of 4 weeks, the clinical improvement of the TCA group (n = 30) was six patients (20%) with no change, one patient (3.3%) with a mild response, 13 patients (43.3%) with a moderate response and 10 patients (33.3%) with a good response. In the cryotherapy group, clinical responses were 12 patients (40%) with no change, four patients (13.3%) with a mild response, 12 patients (40%) with a moderate response and two patients (6.7%) with a good response. There was a statistically significant difference in improvement between the two treatment groups (P = 0.027). According to our results, TCA 40% is more effective for clearance of plantar warts with significantly improved long-term safety profile.