Expandable, gastroretentive dosage forms are promising for precise control of drug concentration in blood. So far, however, short gastric residence times and safety considerations have limited their use. To mitigate such limitations, in this work expandable fibrous dosage forms were investigated for mechanical strength and gastric residence time in dogs. The fiber formulation comprised ibuprofen drug; water-absorbing, high-molecular-weight hydroxypropyl methylcellulose (HPMC) excipient; fiber-strengthening, enteric methacrylic acid-ethyl acrylate excipient; and barium sulfate, a gastrointestinal contrast agent. The fibers were coated either with a hydrophilic sugar, or with a strengthening enteric excipient. Upon administration to a dog, in the stomach the dosage form with sugar-coated fibers expanded to 1.7 times its initial radius in 50–100 minutes, and disintegrated after 4.8 hours. The dosage form with the enteric-excipient-coated fibers, by contrast, expanded to 1.6 times the initial radius in 5 hours, and fractured after 31 hours due to cyclic loads applied by the contracting stomach walls. The fragments passed into the small intestine where they dissolved in less than 2–3 hours. Diametral compression tests and dynamic fatigue failure models show that the substantial increase in gastric residence time is due to strengthening of the fibers by the enteric-excipient coating. Because the enteric excipient is a rubbery semi-solid in the acidic gastric fluid and dissolves in the pH-neutral intestinal fluids, safety concerns should be minimal. Thus, expandable fibrous dosage forms can be readily designed for prolonged, safe gastric retention.