Background: The effectiveness of platelet-rich plasma (PRP) injection in the treatment of lateral epicondylitis remains debatable. Purpose: To evaluate the effectiveness of PRP in lateral epicondylitis treatment using minimal clinically important difference (MCID) values as a reference and to investigate if leukocyte content can influence the effectiveness of the therapy. Study Design: Systematic review; Level of evidence, 4. Methods: Following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-Analyses) guidelines, the authors searched the Medline and Scopus databases for studies on lateral epicondylitis and PRP therapy that used the following patient-reported outcome measures (PROMs): visual analog scale (VAS) for pain; Disabilities of the Arm, Shoulder and Hand (DASH); Patient-Rated Tennis Elbow Evaluation (PRTEE); and Mayo Clinic Performance Index (MAYO). The weighted arithmetic means for the PROMs were calculated at baseline (week 0) and follow-up weeks 4, 8, 12, 24, 52, and 104. The mean differences in outcomes (ΔVAS, ΔDASH, ΔPRTEE, and ΔMAYO) were compared with the MCID values at each follow-up point. In addition, the effectiveness of leukocyte-rich PRP (LR-PRP) versus leukocyte-poor PRP (LP-PRP) was also compared. The Student t test was used in all analyses. Results: A total of 26 studies were included in the analysis. After PRP injection, all PROM scores improved with time. The scores improved significantly from baseline to each follow-up time ( P < .0001), with the exception of the PRTEE (no significant difference at follow-up weeks 12 and 52). The mean difference in scores from baseline exceeded the respective MCIDs from weeks 4 to 104 for the VAS and DASH, from weeks 4 to 52 for the MAYO, and from weeks 8 to 52 for the PRTEE. The MCID for each of the PROMs was exceeded at almost every observation period in both the LR-PRP and the LP-PRP systems. Conclusion: Based on comparisons with the MCID values of commonly used outcome scores, PRP seems to be an effective form of treatment for lateral epicondylitis. Both the LR- PRP and the LP- PRP systems were effective in the context of meeting the MCID.