Prostaglandin analogues (PGAs) have been associated with the development of pseudophakic macular edema (PME) in complicated cataract cases, but evidence on their effects in uncomplicated phacoemulsification remains controversial. This two-arm, prospective, randomised study included patients with glaucoma or ocular hypertension under PGA monotherapy who were scheduled for cataract surgery. The first group continued PGA use (PGA-on), while the second discontinued PGAs for the first postoperative month and reinitiated use afterwards (PGA-off). Topical non-steroidal anti-inflammatory drugs (NSAIDs) were routinely administered to all patients during the first postoperative month. The patients were followed up for three months and the primary outcome was PME development. Secondary outcomes were corrected distance visual acuity (CDVA), central and average macular thickness (CMT and AMT), and intraocular pressure (IOP). The analysis included 22 eyes in the PGA-on group and 33 eyes in the PGA-off group. No patient developed PME. CDVA was not significantly different between the two groups (p= 0.83). CMT and AMT showed a small but statistically significant increase until the end of follow-up (p< 0.001). Mean IOP values had no significant differences between the groups at each visit (p> 0.05). At the end of follow-up, the IOP values were significantly lower than baseline in both groups (p< 0.001). In conclusion, PGA administration with concomitant topical NSAIDs appears to be a safe practice in the early postoperative period of uncomplicated phacoemulsification.