OBJECTIVES We sought to assess the cost implications of two investigation strategies in patients with unexplained syncope. BACKGROUND Establishing a diagnosis in patients with unexplained syncope is complicated by infrequent and unpredictable events. The cost-effectiveness of immediate, prolonged monitoring as an alternative to conventional diagnostic strategies has not been studied. METHODS Sixty patients (age 66 +/- 14 years; 33 males) with unexplained syncope and LV ejection fraction >35% were randomized to conventional testing with an external loop recorder, tilt and electrophysiologic (EP) testing, or prolonged monitoring with an implantable loop recorder with one-year monitoring. If patients remained undiagnosed after their assigned strategy, they were offered a crossover to the alternate strategy. Cost analysis of the two testing strategies was performed. RESULTS Fourteen of 30 patients who were being monitored were diagnosed at a cost of $2,731 +/- $285 per patient and $5,852 +/- $610 per diagnosis. In contrast, only six of 30 conventional patients were diagnosed (20% vs. 47%, p = 0.029), at a cost of $1,683 +/- $505 per patient (p < 0.0001) and $8,414 +/- $2,527 per diagnosis (p < 0.0001). After crossover, a diagnosis was obtained in 1 of 5 patients undergoing conventional testing, compared with 8 of 21 patients who completed monitoring (20% vs. 38%, p = 0.44). Overall, a strategy of monitoring followed by tilt and EP testing was associated with a diagnostic yield of 50%, at a cost of $2,937 +/- $579 per patient and $5,875 +/- $1,159 per diagnosis. Conventional testing followed by monitoring was associated with a diagnostic yield of 47%, at a greater cost of $3,683 +/- $1,490 per patient (p = 0.013) and a greater cost per diagnosis ($7,891 +/- $3,193, p = 0.002). CONCLUSIONS A strategy of primary monitoring is more cost-effective than conventional testing in establishing a diagnosis in recurrent unexplained syncope. (C) 2003 by the American College of Cardiology Foundation.