Purpose <p>The present study evaluated the efficacy of combined use of suprachoroidal injection of triamcinolone acetonide (SCTA) using a modified custom needle with topical nepafenac 0.3% in the treatment of pseudophakic cystoid macular edema (PCME).</p> Methods <p>A prospective randomized study that included sixty eyes of 60 patients with PCME. Patients were divided in two groups, group (1) included 30 patients who received topical nepafenac 0.3% eye drops alone and group (2) that included 30 patients who received a single SCTA (4&#xa0;mg/0.1&#xa0;ml) combined with topical nepafenac 0.3% eye drops.</p> Results <p>In group 1, the central macular thickness (CMT) decreased from 457.4 ± 81.4 um to 252.9 ± 54.6 um after 12&#xa0;months. In respect to group 2, CMT declined from 455.1 ± 79.6 um to 213.7 ± 14.2 um after 12&#xa0;months. The CMT was more significantly reduced in group 2 after 1,3,6,9 and 12&#xa0;months (<i>p</i> value &lt; 0.001). Group 1 showed improvement of best corrected visual acuity (BCVA) by log MAR from 0.9(0.8–1) to 0.2(0.1–0.4) after 12&#xa0;months, while group 2 showed improvement from 0.9(0.8–1) to 0.1(0–0.1) after 12 months. More significant improvement of BCVA was detected in group 2 after 1,3,6 and 9 months with <i>p</i> value &lt; 0.001 and after 12 months with <i>p</i> value 0.001.</p> Conclusion <p>Combined SCTA using this modified custom needle with topical nepafenac 0.3% resulted in better anatomical and functional results in PCME patients compared to topical nepafenac 0.3% alone.</p> <p>The study was prospectively registered with clinical trial.gov ID (NCT04690608) in 27–12-2020.</p>