Aim To determine whether the functional À174 G/C interleukin-6 gene polymorphism is a risk factor for the development of cystoid macular oedema (CMO) following routine uncomplicated phacoemulsification surgery in patients with no established risk factors. Methods A total of 40 patients who underwent routine phacoemulsification surgery as part of a randomised controlled trial comparing the use of postoperative steroid drops against a single sub-tenon injection of triamcinolone were genotyped for the IL-6 À174G/C polymorphism. All patients underwent fluorescein angiography at 30 days and anterior chamber flare measurements pre-operatively and at day 1, 7, and 30. Results Angiographic CMO developed in 14 patients of the 40 studied. 9 out of the 14 patients carried the GG genotype (Fisher's exact test P ¼ 0.05, Hazard ratio for GG genotype; 4.05 (1.02-16.00)). There was no difference in flare measurements between the GG and Non-GG (GC/CC) group. The two groups were otherwise well matched in terms of age, sex, phacoemulsification energy used intraoperatively, and proportion of patients receiving postoperative triamcinolone or steroid drops. Conclusion The À174G/C interleukin-6 promoter gene variant appears to modulate the response to phacoemulsification surgery and to influence the development of postoperative CMO. These data suggest a genetic predisposition to this complication.