Objective: To classify published randomised controlled trials (RCTs) regarding the comparative efficacy and safety of topical glaucoma treatment to identify where the evidence lies and the gaps for future research. Methods: A systematic search of MEDLINE, EMBASE, Cochrane Central and conference proceedings for RCTs recruiting adults with primary open-angle glaucoma (POAG) and/or ocular hypertension (OH) receiving any topical medication or placebo. After double-data entry, the characteristics were analysed with a focus on prostaglandin-containing trials. Results: We identified 510 RCTs. Mean study duration was 15.2 weeks (SD 19.9), with 78% of studies lasting less than three months. Grouping of studies by duration and treatment showed that short-term efficacy was available for all treatments, but RCT evidence of longer-term safety (>12 months) was confined to latanoprost (three trials) and timolol maleate (two trials) in the monotherapy group and dorzolamide and timolol in fixed combination (one trial). The majority of the study population (79.6%) was Caucasian. The data on co-morbidity was sparse. Of prostaglandins, only latanoprost reported hypertension as a sub-group. Latanoprost monotherapy and latanoprost/timolol fixed combination therapy had been compared with the broadest range of alternative therapies. Latanoprost alone had been compared with all other classes of treatments. Conclusion: There are extensive RCT data available for glaucoma treatment. Latanoprost has the most RCTs and is the only prostaglandin analogue with RCTs over 12 months. Other research methodologies (i.e. observational studies) have to be considered alongside RCTs to address important clinical issues like long-term safety and disease progression. There is a lack of RCT evidence to explore differential treatment-effects among subgroups.