Two patients were diagnosed as having unilateral iris pigment epithelial (IPE) cysts that were documented to enlarge and induce angle closure. Transpupillary IPE cystotomies were performed using the Nd:YAG laser as a prophylactic measure to prevent angle-closure glaucoma. Anterior chamber anatomy and cyst dimensions were assessed before, during, and after long-term follow-up using slit-lamp biomicroscopy, gonioscopy, and 20- or 35-MHz high-frequency ultrasound imaging. Cystotomy resulted in immediate, visible deflation of both IPE cysts with subsequent resolution of angle closure. The cyst contents appeared clear and no secondary inflammation or glaucoma occurred. No evidence of cyst recurrence has been noted during 3 and 8 years of follow-up, respectively. Transpupillary Nd:YAG laser cystotomy offered a minimally invasive and effective treatment for angle closure induced by progressive IPE cysts.