PURPOSE:: To describe a case of bilateral cystoid macular edema in a patient with long-standing tramadol hydrochloride use. METHODS:: Observational case report. RESULTS:: A 73-year-old female patient was referred for progressive, bilateral decreased visual acuity. The patient was phakic with a best-corrected visual acuity at presentation was 20/50 on the right eye and 20/64 on the left eye. The patient had a history of low back pain and had been on tramadol hydrochloride 200 mg/day for 16 years. Bilateral cystoid macular edema was confirmed by means of multimodal imaging, including optical coherence tomography angiography. Tramadol intake was progressively reduced over one month and then completely interrupted. At 3 months follow-up, the cystoid macular edema had completely resolved and the best-corrected visual acuity improved in both eyes. CONCLUSION:: Cystoid macular edema may be associated with longstanding treatment with tramadol hydrochloride. Tramadol hydrochloride–associated cystoid macular edema is described and its resolution on tramadol cessation.