Platelet hyperaggregability, known as sticky platelet syndrome (SPS), is a prothrombotic disorder that has been increasingly associated with pregnancy loss. In this retrospective study, we aimed to investigate the clinical and diagnostic relevance of SPS in 208 patients with infertility and unexplained pregnancy loss history. We studied 208 patients that had been referred to undergo a dose-dependent platelet aggregation response to adenosine diphosphate and epinephrine using light transmission aggregometry modified by Mammen during an 11-year period. Patients’ platelet aggregation response was compared with platelet function in 29 female healthy controls of fertile age with no previous history of pregnancy loss. We found a prevalence of SPS type II (33.2%) in 208 female patients with infertility and pregnancy loss. ∆-epinephrine-induced platelet aggregation in patients with SPS was significantly decreased (median 7% and range −21 to 43%) compared to patients without SPS (median 59%, range 7–88% and p < 0.0001) and healthy controls (median 57%, range 8–106% and p < 0.0001). The optimum SPS-diagnostic cutoff value for ∆-epinephrine aggregation was ≤32% (sensitivity 95.7%, specificity 95.2%). SPS patients with low-dose acetylsalicylic acid (ASA) therapy (n = 56) showed improved pregnancy outcome (32 pregnancies; live births n = 18 (56%)) compared to SPS patients without low-dose ASA (n = 13) (3 pregnancies; live births n = 1 (33%)). Our study demonstrates the clinical and diagnostic relevance of platelet hyperaggregation in women with infertility and pregnancy loss history. Further studies should investigate the potential of SPS as a novel decisional tool with both diagnostic and clinical implications in infertility and pregnancy loss.