Background The right ventricular apex (RVA) is the traditional lead site for chronic pacing but in some patients may cause impaired left ventricular (LV) systolic function over time. Comparisons with right ventricular nonapical (RVNA) pacing sites have generated inconsistent results and recent meta-analyses have demonstrated unclear benefit due to heterogeneity across studies. Methods and Results A systematic search for randomized controlled trials that compared LV ejection fraction (LVEF) outcomes between RVNA and RVA pacing was performed up to October 2014. Twenty-four studies (n = 1,628 patients) met the inclusion criteria. To avoid between study heterogeneity two homogenous groups were created; group 1 where studies reported a difference (in favor of RVNA pacing) and group 2 where studies reported no difference between pacing sites. For group 1, weighted mean difference between RVNA and RVA pacing in terms of LVEF at follow-up was 5.40% (95% confidence interval [CI]: 3.94-6.87), related in part to group one's RVA arm demonstrating a significant reduction (mean loss -3.31%; 95% CI: -6.19 to -0.43) in LVEF between study baseline and end of follow-up. Neither of these finding were seen in group 2. Weighted regression modeling demonstrated that inclusion of poor baseline LVEF (<40%) in combination with greater than 12 months follow-up was three times more common in group 1 compared to group 2 (weighted relative risk 2.82; 95% CI: 1.03-7.72; P = 0.043). Conclusions In patients requiring chronic right ventricular pacing where there is inclusion of impaired baseline LVEF (<40%), RVA pacing is associated with deterioration in LV function relative to RVNA pacing.