Abstract Background In-hospital acquired thrombocytopenia (TP) is relatively common among patients hospitalized with acute coronary syndromes (ACS). However, its effect on short-term and long-term outcomes has yet to be reviewed systematically. Methods We conducted a systematic review and meta-analysis of clinical studies assessing the relationship between new-onset in-hospital TP and adverse outcomes among ACS patients. MEDLINE, Scopus and the Cochrane Library were searched for eligible studies published before March 20, 2016. Results Ten studies reporting on a total of 142,161 ACS patients were identified. 8133 patients showed evidence of new-onset TP during the course of their hospitalization. Compared with patients with normal platelet counts, patients with new-onset TP had a prolonged in-hospital stay, significantly higher risk of both short-term mortality (< 30 days) (Odds ratio (OR) 95% confidence interval (CI): 5.58 3.63–8.57) and late death (6 months to 1 year) (OR 95%CI: 3.45 2.35–5.07), as well as a significantly higher risk of major bleeding events in the first 30 days (OR 95%CI: 6.93 5.13–9.38). In addition, risk for other secondary cardiovascular endpoints, including recurrent myocardial infarction, stroke, in-hospital heart failure, stent thrombosis and unplanned revascularization was also significantly higher in the TP versus the no TP group. Conclusions Development of TP during the in-hospital management of ACS patients is a significant predictor of both short- and long-term adverse events, including mortality. In the light of this evidence, clinicians should be cautious and closely monitor abnormal platelet counts that present early following an ACS.