The purpose of the TRENDS trial was to assess the safety, efficacy, and cost effectiveness of a no-predilatation ("direct") stenting strategy in the treatment of de novo native coronary artery lesions using the Multilink Tetra stent system. In this multicenter, prospective clinical trial, 1,000 patients were randomized (1:1) to receive a Multilink Tetra stent with or without balloon predilatation. The primary outcome measurement was major adverse cardiac events (MACEs) at 30 days; secondary end points included resource utilization (including procedural duration, equipment use, and length of hospital stay), MACEs, and angiographic binary restenosis at 180 days. In the predilatation group, 587 stents were implanted in 499 patients; in the direct group, 579 stents were implanted in 501 patients. In the direct group, stents in 31 lesions (5.7%) required predilatation and multivariate analysis identified calcification (odds ratio 5.81), angulation (odds ratio 5.34), and preprocedural minimal lumen diameter (odds ratio 0.09) as direct stenting failure. MACEs at 30 days were similar in the 2 groups, with 19 (3.8%) in the predilatation group and 13 (2.6%) in the direct group (p = NS). Resource utilization favored the direct strategy, with decreases in balloon use, contrast media, and procedure time, but a larger number of guiding catheters was used. The 180-day MACE rate of 9.8% in the direct group was not significantly less than the rate of 10.8% in the predilatation group (p = NS). Quantitative angiographic follow-up at 6 months demonstrated in-stent binary restenotic rates of 11.4% in the predilatation group (late loss 0.88 +/- 0.53 mm) and 12.3% in the direct group (late loss 0.82 +/- 0.51 mm, p = NS) and in-segment restenosis rates of 12.2% and 13.4%, respectively (p = NS). In conclusion, a direct stenting strategy with the Multilink Tetra stent was feasible and safe in 94% of lesions and associated with lower resource utilization compared with a predilatation approach. Direct stenting was not associated with significantly lower MACE and target lesion revascularization rates and had no effect on late angiographic follow-up, with similar late loss reflecting an identical biologic response to bare metal stent placement.