Purpose: A meta-analysis of observational studies was conducted to evaluate the effect of prostaglandin analogues (PGAs) on central cornea thickness (CCT) of patients with glaucoma and ocular hypertension (OHT). Methods: A literature search was performed through Pubmed, Embase, Cochrane Library, the System for Information on Grey Literature in Europe (Open Grey), ClinicalTrials.gov, and reference lists of retrieved studies. Observational studies were included in our meta-analysis. The final CCT of patients and 95% confidence interval (CI) from each study were extracted. Study quality was assessed using The Newcastle-Ottawa Scale (NOS) and the Agency for Healthcare Research and Quality (AHRQ). A fixed-effects model was used to calculate the weighted mean difference (WMD) and 95% confidence interval (CI). Subgroup analyses based on several stratified factors were also performed. Results: Five cohort studies, five case-control, three cross-sectional studies involving 2722 subjects were included. The pooled effect of all thirteen studies showed PGAs can reduce CCT of patients with glaucoma or OHT slightly but significantly (WMD, -9.37; 95% CI [-12.18, -6.57], P =0.00; I2 = 45.5%). And significant results were observed in all specific study design ( WMD, -5.17; 95% CI [-9.52, -0.82] for cohort study; WMD, -15.31; 95% CI [-22.66, -7.97] for case–control study; WMD, -8.65; 95% CI [-17.30, -0.01] for cross-sectional study). Also, subgroup analysis of exposure time showed the effect of PGAs was more obvious in the first two years (WMD, -5.81; 95% CI [-9.49, -2.14] for 1 year; WMD, -13.02; 95% CI [-20.03, -6.01] for 2 years). Conclusions: The pooled effects from current literature suggest that PGAs use could reduce CCT of patients with glaucoma or OHT slightly but significantly, and this effect is more pronounced in the first two years. This reminds us that we need to pay attention to the changes in CCT during the first two years of PGA use in case we misestimate intraocular pressure (IOP) and the efficacy of the PGA.