Background: Warts are benign proliferations 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 intralesional 5-FU solution and 5-FU solution using micro needling technique in the treatment of planter warts. Patients and methods: Our study was carried out on 60 patients complaining of planter warts divided into two equal groups: A and B from June 2020 to Janurary 2021, Group A: with planter warts received intralesional 5-FU solution every two weeks, and Group B:with planter warts received 5-FU solution using a micro needling pen type device every two weeks, for maximum period of six sessions or complete absence of the lesion. 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 21 patients (70%) in group A and 25 patients (83.3%) in group B. Partial cure rates occurred in4 patients (13.3%) in group A, and2 patients (6.7%) in group B after 12 weeks of treatment. No response occurred in 5 patients (16.7%) in group A, and 3 patients (10%) in group B. Most of partial and nonresponsive patients had lesions of mosaic type infection. Conclusion: Derma pen use in the treatment of planter warts by 5- fluorouracil solution 50 mg/ml was superior to intralesional injection of the same medication.