Background: Isotretinoin, an oral retinoid, is the most effective acne therapy. Isotretinoin has proven superior to other acne treatments. It is critical for clinicians to be aware of the side effects, toxicities, and management concerns associated with its usage. Objective: To evaluate the most common side effects while using isotretinoin therapy in acne in Egyptian female in Dakahlia. Patients and methods: Cohort, prospective, experimental study was conducted at Dermatology, Andrology and STDs outpatient clinic of Mansoura University Hospital on 80 female patients with acne who received isotretinoin therapy for three months, during the duration from February 2023 to October 2023.Results: After 1 month of treatment, the highest reported side effect was dry lip (92.5%), xerosis of skin at 35.0%, dry eyes increased to 28.8%, followed by dryness of mucous membrane (13.8%), hair loss (8.8%), facial erythema at 3.8%, sun sensitivity (2.5%), epistaxis (1.3%), irregular menses 5%, while mood changes and tiredness, headache, muscle ache, and abdominal pain were reported at 1.3% each. After 3 months, the most prevalent side effects were dry lips (100%), xerosis at 73.8%, dry eyes and mood changes reported (63.8%) for each, tiredness (52.5%), dryness of mucous membrane (51.3%), joint ache (47.5%), hair loss (42.5%), irregular menses (40%), muscle ache (37.5%), and facial erythema at 33.8%. Conclusion: The most common side effects were dry lips, dry eyes, irregular menses and hair loss. There was a significant relationship between higher dose of isotretinoin and severity of acne vulgaris with the presence of diarrhea. Isotretinoin appeared to have a bigger effect on lipids than on liver enzymes, and we suggested using isotretinoin with close monitoring.