OBJECTIVES: In 2011/2012, a single-blind, cluster randomised controlled trial (RCT) was conducted in a tertiary referral Irish hospital to evaluate the Screening Tool of Older Persons’ Prescriptions (STOPP) and Screening Tool to Alert Right Treatment (START) criteria compared to usual hospital care. This intervention demonstrated positive outcomes in terms of reduction of adverse drug reactions (ADRs). The aim of this study was to compare the cost-effectiveness of a physician implementing the STOPP/START criteria to unselected older hospitalised patients in 2011/2012 with the cost-effectiveness of this intervention if applied within the Irish hospital setting using the most currently available (2015) healthcare costs (CAHC). METHODS: Cost-effectiveness analysis (CE) alongside conventional outcome analysis in a cluster RCT. The screening tool was applied to medicines of intervention arm patients (n= 360); control arm patients (n= 372) received routine medical care. Incremental cost-effectiveness was examined in terms of 2011/2012 costs and CAHC to the Irish healthcare system and an outcome measure of ADRs during an inpatient hospital stay in 2011/2012. Uncertainty in the analysis was explored using a cost-effectiveness acceptability curve (CEAC). RESULTS: On average, the intervention arm was more costly but was also more effective for both 2011/2012 costs and CAHC. The associated incremental cost-effectiveness ratios (ICER) per ADR averted were €5,358 and €5,469 applying 2011/2012 costs and CAHC respectively. The probability of the intervention being cost-effective in 2011/2012 at threshold values of €0, €10,000 and €20,000 was 0.236, 0.680 and 0.926 respectively. The probability of the intervention being cost-effective using CAHC at threshold values of €0, €10,000 and €20,000 was 0.236, 0.672 and 0.921 respectively. CONCLUSIONS: Despite intervention implementation having a slightly greater ICER when using CAHC, such accompanying ADR reductions may possibly result in satisfactory savings and greater patient outcomes. Healthcare policy makers should consider the adoption of the STOPP/START criteria in routine hospital care.