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Patients with thrombotic antiphospholipid syndrome (APS) or subjects with persistent presence of antiphospholipid antibodies (aPLA), defined “carriers”, may develop thrombocytopenia. However, the prevalence and clinical characteristics associated with thrombocytopenia remain poorly understood. We aimed to describe the prevalence and the clinical characteristics associated with thrombocytopenia in APS patients and aPLA carriers included in the Survey on AnTicoAgulated Patients-RegisTry on antiphospholipid antibodies (START-APS), a multicentre prospective registry. Thrombocytopenia was defined as a platelet count < 150 × 109/L, while moderate-to-severe form was defined as < 100 × 109/L. Logistic regression analysis was performed, and results were expressed as Odds Ratio (OR) and 95% confidence interval (95%CI). A total of 464 patients were included (148 aPLA carriers, 316 APS), mean age was 57.3 ± 15.6 years, and 66.5% were women. 63 (13.6%) patients presented with thrombocytopenia; 15.2% in APS patients and 10.1% in aPLA carriers (p = 0.138). Overall, triple positive pattern (OR 1.90, p = 0.002), livedo reticularis (OR 3.57, p = 0.029), heart failure (OR 4.52, p = 0.039), and female sex (OR 0.59, p = 0.011) were associated with thrombocytopenia. Triple positivity (OR 5.44, p < 0.001) and history of myocardial infarction (OR 6.52, p = 0.009) were associated with moderate-to-severe thrombocytopenia. Thrombocytopenia may occur early also in aPLA carriers, raising to 15% in APS patients, especially in those presenting with triple positivity and cardiovascular involvement. This association was confirmed also with moderate-to-severe thrombocytopenia.