This study aimed to evaluate the efficacy of angiotensin-converting enzyme inhibitors (ACEi) in preventing anthracycline-induced cardiotoxicity in patients undergoing anthracycline-based chemotherapy. PubMed, Embase, and Cochrane databases were searched for randomized controlled trials (RCTs) comparing ACEi with standard treatment/placebo for cardiotoxicity prevention in patients undergoing anthracycline-based chemotherapy. We pooled outcomes of echocardiographic and cardiac biomarker changes. A random-effects model was used for all outcomes. We included 7 RCTs with 686 patients, of whom 346 (50%) received prophylaxis with ACEi. The most common malignancy was breast cancer, and the follow-up ranged from 6 to 31 months. Prophylactic use of ACEi was associated with a significantly smaller reduction in left ventricular ejection fraction (LVEF) compared with the control group {mean difference (MD) -5% [95% confidence interval (CI) -8% to -2%]; P < 0.010}. Subgroup analysis limited to studies excluding trastuzumab from the chemotherapy regimens showed no significant difference [MD -7% (95% CI -16% to 2%); P = 0.110]. By contrast, in studies including trastuzumab-containing regimens, ACEi demonstrated a statistically significant effect in limiting LVEF reduction [MD -3%, (95% CI -4 to -1); P < 0.010]. Diastolic function (E/A ratio) changes [MD 0.0 (95% CI -0.1 to 0.09); I 2 = 36.3%] and relative risk of increased troponin I at follow-up [Risk-Ratios 0.58 (95% CI 0.17-1.94); I 2 = 69.6%] were not statistically significant. Prophylactic ACEi administration in patients undergoing anthracycline-based chemotherapy was associated with a smaller decline in LVEF. This protective role may be more relevant in patients also receiving trastuzumab. More powered and longer follow-up studies are needed to confirm these findings.