Zofran will take 20 to 30 minutes to start showing its antiemetic and sickness improvement effects. It will maximum take 2 to 2 and a half hours to show its full effects. It largely depends on the dosage form as well. If the dosage form is injectable (100% bioavailability), you will see sudden effects as compared to tablets that are taken orally. It is usually prescribed to take Zofran before mealtime to avoid any nausea-like symptoms.