OBJECTIVES: Safety and efficacy of tafluprost for open-angle glaucoma or ocular hypertension (OH) have been proven in clinical trials. While tafluprost and latanoprost have similar efficacy, the absence of the preservative benzalkonium chloride (BAK) in tafluprost may make it a preferred alternative for patients who are intolerant to BAK (i.e., reduces adverse ocular symptoms such as irritation and dry eye). Reduced ocular symptoms offer clinical/QoL benefits and cost savings associated with less rescue medication use (artificial tears). Further, the single-dose unit formulation of tafluprost is predicted to lessen medication wastage and thus generate cost savings versus latanoprost (dispensed in multi-dose bottles). These cost-savings are quantified and cost-effectiveness ratios are calculated in the current study.     METHODS: Resource usage and associated costs are quantified to determine cost savings offered by tafluprost over latanoprost. Disutility from adverse ocular symptoms caused by preservatives is also determined via a systematic review of literature to transform tafluprost’s superior tolerability to QALYs. The perspective of this analysis is the Australian health care system. RESULTS: Preservative-free tafluprost was shown to be a highly cost-effective, most likely dominant, strategy over preserved latanoprost. The likely cost savings due to reduced medication wastage, informed by the pattern of latanoprost utilisation observed in the Australian drug reimbursement system (PBS), in itself would make tafluprost a cost-saving strategy versus latanoprost. The available evidence suggested that 47.6% of patients on preserved latanoprost experience some adverse ocular symptoms, while this is expected to be 29.0% with preservative-free tafluprost. Average cost savings attributable to reduced artificial tear use was estimated to be $23.64 per patient per year. This superior tolerability is also estimated to produce an incremental QALY of 0.0107 for preservative-free tafluprost each year when compared with preserved latanoprost. CONCLUSIONS: Preservative-free tafluprost is a highly cost-effective, most likely dominant, strategy over preserved latanoprost.