Background: This prospective study investigated the association between preprocedural biomarker levels and incident major adverse cardiac events (MACE) in complex patients undergoing percutaneous coronary intervention (PCI) with sirolimus-eluting stenting. Hypothesis: Lipoprotein(a) (Lp[a]), interleukin-10 (IL-10), and high-sensitivity C-reactive protein (CRP) have long-term prognostic value in patients undergoing PCI. Methods: Between April 2002 and February 2003, 161 patients were included in the study. Blood was drawn before the procedure, and biomarkers were measured. Patients were followed-up for MACE (death, nonfatal myocardial infarction, and repeat revascularization). Cox proportional hazard models were used to determine risk of MACE for tertiles of biomarkers. Both 1-year and long-term follow-up (median, 6 years; maximum, 8 years) were evaluated. Results: Mean age was 59 years, and 68% were men. During long-term follow-up, 72 MACE occurred (overall crude cumulative incidence: 45% [95% confidence interval (CI): 37%-52%]). Lp(a) was associated with a higher 1-year risk of MACE, with an adjusted hazard ratio (HR) of 3.1 (95% CI: 1.1-8.6) for the highest vs the lowest tertile. This association weakened and lost significance with long-term follow-up. IL-10 showed a tendency toward an association with MACE. The 1-year HR was 2.1 (95% CI: 0.92-5.0). Long-term follow-up rendered a similar result. The association of CRP with MACE did not reach statistical significance at 1-year follow-up. However, CRP was associated with long-term risk of MACE, with an HR of 1.9 (95% CI: 1.0-3.5). Conclusions: In this prospective study, preprocedural Lp(a) level was associated with short-term prognosis after PCI. The preprocedural CRP level was associated with long-term prognosis after PCI. Clin. Cardiol. 2012 DOI: 10.1002/clc.21988 The authors have no funding, financial relationships, or conflicts of interest to disclose.