OBJECTIVES: To evaluate the cost-effectiveness of diagnosis with an ILR following Standard Testing (ST) after a syncopal event from a USA payer perspective. METHODS: This analysis considers all costs of diagnosis via ST and ILR, the costs and consequences of recurrent syncope, and the cost of arrhythmia treatment following diagnosis. A Markov model was developed to reflect the recurrence of syncopal events in undiagnosed patients. Due to documented differences in the prevalence of arrhythmia between patients with suspected arrhythmia and patients with unexplained syncope we considered the two populations separately, each over a 10-year time horizon. All costs and consequences were discounted at a 3% annual rate. RESULTS: The results are similar for suspected arrhythmia and unexplained syncope. In the suspected arrhythmia population, the incremental cost of the ILR strategy is $14,712. The incremental Quality Adjusted Life Years (QALY) are estimated to be between 0.2806 and 0.4282, and the incremental cost-effectiveness ratio (ICER) is between $34,400 and $52,400. The syncopal events avoided with ILR are 402 per 1,000 patients. In the unexplained syncope population the incremental costs and effects are lower compared to the previous case: $13,800, and between 0.2174 and 0.3317 QALYs gained. The ICER is between $41,600 and $63,500 per QALY gained. The number of syncopal events avoided with ILR is 311 per 1,000 patients. In 1,000 patients the ILR strategy is estimated to identify between 300 and 380 more arrhythmia cases compared to ST in the two populations. CONCLUSIONS: When considering all costs in combination with the syncopal events avoided and quality of life (QoL), ILR arrhythmia diagnosis is a cost-effective alternative to ST. The use of ILR increases the diagnostic yield in both populations and guides treatment in more patients compared to ST.