Yes, Zofran (ondansetron) can be taken on an empty stomach. It is effective whether taken with or without food. In fact, some sources note that it may work faster when taken on an empty stomach, such as about an hour before eating. There is no harm in taking Zofran without food, and you can use the oral solution, orally disintegrating tablets, or regular tablets without concern about meals. Always follow the dosing instructions provided by your healthcare provider for best results.