Objectives: Preservatives contained in glaucoma eye drops have been shown to have a deleterious impact on the ocular surface. This study aimed to assess the influence of preservatives on the occurrence of further glaucoma surgery among patients with glaucoma or ocular hypertension in France. Methods: This retrospective cohort study consisted of an analysis of data from a French medical-administrative database (Échantillon Généraliste des Bénéficiaires (EGB)). The study concerned all patients who first received glaucoma eye drops treatments in the EGB database between 2008 and 2016 and received at least 3 months of treatment claim within the first year of follow-up. Three groups were created according to the level of preservative consumption during the whole follow-up: “0% preservatives”, “mixed” and “100% preservatives”. The risk of glaucoma surgery was estimated according to preservative exposure group in Cox multivariate models. The adjustment variables were age, sex, number of glaucoma eye drops classes, use of systemic anti-hypertensive treatment, and duration of exposure to intraocular pressure (IOP)-lowering agents. Results: The sample consisted of 12,454 patients firstly treated for glaucoma or ocular hypertension between January 2008 and December 2015. The median (interquartile range) follow-up was 4.1 (1.7-6.1) years. A total of 231 (1.9%) patients underwent glaucoma surgery during follow-up. On multivariable analysis, the risk of glaucoma surgery was increased for the “100% preservative” group (HR=7.97 [95% CI, 3.07-20.67]) and for the “mixed” group (hazard ratio [HR] = 3.94 [95% CI, 1.54-10.05]) when compared with the 0% preservatives group. Conclusions: We found an association between exposure to glaucoma eye drops preservatives and the occurrence of further glaucoma surgery. In real life, these results support the use of preservative-free glaucoma eye drops among a large sample of patients in a long-term basis.