Purpose <p>Endometrial platelet-rich plasma (PRP) is proposed to treat thin endometrium and implantation failure. Different techniques are described, and nomenclature is often confusing, with infusion or injection being used interchangeably, not discriminating between methods. Sub-endometrial injection, by hysteroscopic or ultrasound guidance, differs from intracavity infusion, but whether this method is superior has not been subject to review.</p> Methods <p>A systematic review and meta-analysis was performed to compare sub-endometrial injection against placebo or intra-cavity infusion in a defined assisted reproduction population, with subgroup analysis to assess for any differences between USS-guided or Hysteroscopic Techniques. Primary outcomes were clinical pregnancy (CPR), live birth (LBR), and miscarriage rates (MR).</p> Results <p>Significant increases in CPR (OR = 5.14, <i>p</i> &lt; 0.001) and LBR (OR = 4.60, <i>p</i> &lt; 0.001) were seen in appropriately selected patients with sub-endometrial PRP injection compared to placebo, with a reduction in MR (OR = 0.60, <i>p</i> = 0.036). The benefit of injection compared to infusion appears highest for CPR in those with a resistant thin endometrium (<i>p</i> = 0.03).</p> Conclusions <p>Sub-endometrial administration may improve the efficacy of PRP in selected patients. More work is needed to identify the optimal candidates, and given the additional administration challenges, whether injection should be a first-line intervention, or considered after unsuccessful infusion, remains open to debate, with more studies needed to confirm this.</p>