Background: There are ongoing attempts to find a reliable, highly sensitive and specific early indicator of myocardial ischemia. Recently, a potential new function for the “non-pregnancy”-related pregnancy-associated plasma protein-A (PAPP-A) protein has been reported in many papers, including that the protein could be used in diagnosing heart conditions. Hence, our study aimed to determine the diagnostic and prognostic significance of PAPP-A protein in individuals diagnosed with non-ST-elevation acute coronary syndromes (NSTE-ACSs). Methods: The study comprised 100 consecutive patients (68 males and 32 females), aged from 42 to 83 years (mean age: 64.2 years). We assessed PAPP-A protein levels, anthropometric measurements, basic laboratory tests, ECG recordings, and coronary angiography for each patient. The participants were subsequently divided into two groups: non-ST-elevation myocardial infarction (NSTEMI, n = 74) or unstable angina (UA, n = 25). Results: The levels of PAPP-A protein in patients with NSTEMI were slightly higher than those in patients with UA, but the difference was not statistically significant (7.93 ± 6.35 mIU/L vs. 6.52 ± 5.45 mIU/L, p = 0.253). Higher PAPP-A protein levels (≥5.83 mIU/L) were associated with a numerically higher, but not statistically significant, risk of NSTEMI (OR = 1.37; 95% CI: 0.56–3.36). After 12 months, there was a significant correlation between the amount of labelled PAPP-A protein and the likelihood of experiencing acute myocardial infarction, cardiovascular death, and the necessity for unplanned coronary angiography. Conclusions: The diagnostic utility of PAPP-A protein in NSTE-ACS is limited, both in the NSTEMI and UA patient groups. However, its measurement can be used to estimate the annual risk for these groups of patients.