Background: High inflation pressure (HP) after coronary stent deployment has become a standard approach because it has been associated with a decreased subacute stent thrombosis (SAT) rate. However, the impact of HP on long-term outcomes is still unclear. We compared the long-term results of a strategy of increasing HP (≥12 atm) until the achievement of angiographic success (<20% residual stenosis) with a prespecified very high inflation pressure (VHP) strategy of 20 atm without intermediate inflations. Methods and Results: We conducted a parallel-group, nonrandomized study to evaluate the short- and long-term results in 136 consecutive eligible patients who underwent successful single Palmaz-Schatz stent implantation in vessels ≥3 mm. Major adverse cardiac events (MACE), that is, death, myocardial infarction, and target lesion revascularization (TLR), were monitored for a minimum of 6 months. No significant differences were observed between the two strategies in terms of final minimal lumen diameter (HP, 3.0 ± 0.5 vs VHP, 3.1 ± 0.5 mm) and acute gain (HP, 2.1 ± 0.7 vs VHP, 2.2 ± 0.6). The overall rate of subacute stent thrombosis was 0.7%. During a 405 ± 148-day follow-up, 21 (28.8%) patients in the VHP group and 6 (9.5%) in the HP group (P = .005) had MACE, with a TLR rate of 27.4% versus 7.9% (P = .009), respectively. By multivariate analysis, the use of VHP increased the odds of long-term MACE by a factor of 3.48 (P = .009). Among patients undergoing TLR, those treated with VHP had a greater lumen loss (HP, 1.83 ± 0.57 vs VHP, 2.15 ± 0.36 mm, P = .02) and a more frequent pattern of diffuse restenosis (71% vs 16%, P = .06). Conclusions: In our study, the two strategies had similar acute and short-term results, but VHP was associated with a poorer long-term outcome. These data provide a rationale for a less aggressive strategy for stent deployment by optimizing rather than attempting to maximize inflation pressure and stent expansion.