The association between lipoprotein (a) (Lp(a)) and 10-year first fatal/nonfatal cardiovascular disease (CVD) risk in apparently healthy men and women was evaluated. The ATTICA prospective study was conducted during 2001-2012 and included n = 1514 men and n = 1528 women (age >18 years) from the greater Athens area, Greece. Follow-up CVD assessment (2011-2012) was achieved in n = 2020 participants (n = 317 cases); baseline Lp(a) was measured in n = 1890 participants. The recommended threshold of 50 mg/dL was used to define abnormal Lp(a) status. Ten-year CVD-event rate was 14% and 24% in participants with Lp(a) <50 and Lp(a) ≥50 mg/dL, respectively. Multivariate analysis revealed that participants with Lp(a) ≥50 mg/dL versus Lp(a) <50 mg/dL had about 2 times higher CVD risk (hazard ratio (HR) = 2.18, 95% confidence interval (CI) 1.11, 4.28). The sex-based analysis revealed that the independent Lp(a) effect was retained only in men (HR = 2.00, 95% CI 1.19, 2.56); in women, significance was lost after adjusting for lipid markers. Sensitivity analyses revealed that Lp(a) increased CVD risk only in case of abnormal high-density lipoprotein cholesterol, apolipoprotein A1, and triglycerides as well as low adherence to Mediterranean diet. Certain patient characteristics may be relevant when considering Lp(a) as a therapeutic or risk-prediction target.