Observational studies have shown promising therapeutic effects of long-pulsed neodymium-doped yttrium aluminum garnet (LP-Nd:YAG) laser on warts.To evaluate whether LP-Nd:YAG laser was superior to cryotherapy for cutaneous warts.In this study, 150 adult patients with warts were randomized equally to receive laser or cryotherapy every 3-4 weeks, a maximum of 4 sessions. The primary outcomes were cure rate at 16 weeks and 6 months; secondary outcomes included time to clearance of warts and treatment-related adverse effects.There was no difference in the cure rate for laser versus cryotherapy at 16 weeks (54.1% vs. 46.7%) and 6 months (59.5% vs. 57.3%). However, time to clearance of warts, up to 16 weeks and 6 months, tended to be shorter for laser versus cryotherapy ( P = .04 and .08, respectively). Post-hoc analyses showed a significantly higher cure rate for laser versus cryotherapy in 3 subgroups of HPV 2/27/57-induced recalcitrant warts, but not in their counterpart subgroups. Laser had more mild adverse effects.Single-center.The overall therapeutic effects of LP-Nd:YAG laser were similar to cryotherapy, but laser may be more effective to relatively recalcitrant warts and may associate with shorter time to clearance of warts.