To our knowledge, we are reporting the first case of a 59-year-old man who developed recurrent CME with three separate trials of three different prostaglandin class drugs following uncomplicated phacoemulsification with intraocular lens implantation. Despite multiple reports of individual prostaglandin (PG) analogues being suggested as the cause of CME, there are no recommendations regarding withholding these medications in the perioperative period. Our patient first developed CME OD 4-months post uncomplicated cataract extraction. XALATAN (Latanoprost) had been restarted after surgery and discontinued at onset of CME. While off XALATAN (Latanoprost), the patient's CME resolved, but his IOP rose. The patient was started on LUMIGAN (Bimatoprost) to control the IOP, but within weeks his CME recurred. The patient's CME was again treated and his IOP remained acceptable, but then progressively increased. TRAVATAN (Travoprost) was attempted, but he presented with a third round of CME. Definitive conclusions about causal relationships cannot be made without well-designed, prospective clinical trials addressing this issue.