The Strategy for Intravascular Ultrasound (IVUS) guided PTCA and Stenting trial included a prospectively designed economic analysis to investigate whether routine IVUS guidance intervention is cost-effective. Consecutive patients (n = 269) with 356 lesions were randomly assigned to receive provisional stenting with angiographic guidance only (ANGIO) or with IVUS guidance. The 2-year major adverse cardiac event-free survival (effectiveness) was significantly higher in the IVUS-guided group (80% vs 69%, p <0.04). In-hospital costs for procedural personnel, capital equipment, and disposable equipment were higher in the IVUS group. This was offset by lower costs for inpatient care and urgent target vessel revascularization in the IVUS group. Therefore, the total in-hospital cost was only slightly higher with IVUS (5,245 ± $2,256 [IVUS] vs 4,776 ± $2,961 [ANGIO], $/patient, p = 0.15). During a 2-year follow-up, costs for cardiac hospitalizations were slightly lower in the IVUS group, whereas costs for medication and indirect costs were similar. This resulted in identical total costs over the 2-year period (15,947 ± $8,545 [IVUS] vs 16,103 ± $9,954 [ANGIO], $/patient, p = 0.89). The incremental cost-effectiveness ratio for IVUS guidance calculated to −$1,417/major adverse cardiac event-free survival gained. In 55.3% of bootstrapping replications, IVUS was less expensive and more effective. In conclusion, when used in a provisional stenting strategy, routine IVUS imaging is cost-saving half the time.