Background Premature ventricular complexes (PVCs) are a potentially reversible cause of heart failure. However, the characteristics of patients most likely to develop impaired left ventricular function are unclear. Hence, the objective of this study is to systematically assess risk factors for the development of PVC-induced cardiomyopathy. Methods We performed a structured database search of the scientific literature for studies investigating risk factors for the development of PVC-induced cardiomyopathy (PVC-CM). We investigated the reporting of PVC-CM risk factors (RF) and assessed the comparative association of the different RF using random-effect meta-analysis. Results A total of 26 studies (9 prospective and 17 retrospective studies) involving 16,764,641 patients were analyzed (mean age 55 years, 58% women, mean PVC burden 17%). Eleven RF were suitable for quantitative analysis (≥ 3 occurrences in multivariable model assessing a binary change in left ventricular (LV) function). Among these, age (OR 1.02 per increase in the year of age, 95% CI [1.01, 1.02]), the presence of symptoms (OR 0.18, 95% CI [0.05, 0.64]), non-sustained ventricular tachycardias (VT) (OR 3.01, 95% CI [1.39, 6.50]), LV origin (OR 2.20, 95% CI [1.14, 4.23]), epicardial origin (OR 4.72, 95% CI [1.81, 12.34]), the presence of interpolation (OR 4.93, 95% CI [1.66, 14.69]), PVC duration (OR 1.05 per ms increase in QRS-PVC duration [1.004; 1.096]), and PVC burden (OR 1.06, 95% CI [1.04, 1.08]) were all significantly associated with PVC-CM. Conclusions In this meta-analysis, the most consistent risk factors for PVC-CM were age, non-sustained VT, LV, epicardial origin, interpolation, and PVC burden, whereas the presence of symptoms significantly reduced the risk. These findings help tailor stringent follow-up of patients presenting with frequent PVCs and normal LV function.