Yes, you should take Orlistat with food. For the medication to work, take one capsule with water immediately before, during, or up to one hour after each of your three main meals. Crucially, the meal must contain some dietary fat for Orlistat to be effective. If you skip a main meal, or if your meal contains absolutely no fat, you can safely skip that dose. To minimize mild digestive side effects, ensure your daily fat intake is evenly distributed across your three main meals and does not exceed about 30% of your total daily calories.