Purpose: To report the first case of acute angle closure due to a high-pressure Descemet membrane detachment following deep anterior lamellar keratoplasty (DALK) using the “big bubble” technique. Observations: A 25-year-old man underwent DALK surgery for keratoconus using the “big bubble” technique in which an air bubble is injected in deep stroma to promote dissection of underlying Descemet membrane from stroma. Surgery was uneventful and the patient was discharged home in good conditions. On post-operative day 1, the patient came back with severe periocular pain. Intra-ocular pressure was found to be 38 mmHg. Anterior-segment OCT revealed a “double anterior chamber” created by a high-pressure Descemet detachment that was occluding the pupil and causing secondary acute angle closure glaucoma. The patient was brought back promptly to the operating room where the high-pressure chamber was properly evacuated, allowing Descemet membrane to properly reattach to stroma. Conclusions and importance: Inability to recognize stroma from Descemet membrane during the dissection of the “big bubble technique” can result in failure to evacuate the high-pressure Descemet membrane detachment, putting the patient at risk for acute angle closure glaucoma from occlusion of the pupil. Proper dissection of stroma from underlying DM is a challenging and crucial step in the “big bubble” technique. Several methods, such as the injection of small bubbles in the anterior chamber or the use of intra-operative anterior segment OCT could be employed to prevent such a complication.