Background: Warts are benign proliferation of skin and mucosa that result from infection with human papilloma virus (HPV) which are double stranded deoxyribonucleic acid (DNA) viruses that replicate inside the nucleus. Infection with HPV may be clinical, subclinical, or latent. Objective: To compare the efficacy and safety of potassium hydroxide 30% (KOH) versus trichloroacetic acid 30% (TCA) in treatment of plane warts. Patients and methods: Our study was carried out on 60 patients complaining of plane warts divided into A and B from November 2019 to March 2020, Group A: thirty patients treated by potassium hydroxide (KOH 30%) weekly and Group B: thirty patients treated by trichloroacetic acid (TCA 30%) weekly for maximum period of 12 weeks, with pointed end of a wooden applicator to the center of all the lesions until a white frost appeared. Patients were selected from out-patient clinic of Dermatology, Venereology and Andrology Department of Al-Azhar University Hospitals. Results: The present study showed complete cure rates of 7 patients (23.3%) in group A and 7 patients (23.3%) in group B. Partial cure rates occurred in 15 patients (50%) in group A and 16 patients (53,3%) in group B after 12 weeks of treatment. No response occurred in 8 patients (27.6%) in group A and 7 patients (23.3%) in group B. All nonresponsive patients had lesions in sites other than face except for 2 patients, one in each group had facial lesions. Conclusion: Based on our findings, both potassium hydroxide (KOH 30%) and trichloroacetic acid (TCA30%) are equally effective in treatment of plane warts without statistically significant difference at end of treatment period and follow up, but TCA (30%) was safer than KOH (30%).