Platelet-rich plasma (PRP) is an autologous preparation used to accelerate regeneration; however, this form of therapy is not always effective. Vascular endothelial growth factor B (VEGFB), which affects vessel survival, pathological angiogenesis, and muscle development may differentiate the risk and treatment of lateral elbow tendinopathy (LET). In this study, we analyzed the influence of VEGFB gene polymorphisms on the effectiveness of LET treatment with PRP. Therapeutic effectiveness was analyzed in 107 patients (132 elbows) using patient-reported outcome measures (PROMs), specifically the visual analog scale (VAS); quick version of disabilities of the arm, shoulder, and hand score (QDASH); and patient-rated tennis elbow evaluation (PRTEE), for two years (weeks 2, 4, 8, 12, 24, 52, and 104). The polymorphisms selected for the study were rs72922019, rs12366035, rs4930152, rs594942, and rs595880, being in strong linkage disequilibrium. Patients with TT (rs72922019), TT (rs12366035), AA (rs4930152), CC (rs594942), and GG (rs595880) genotypes showed better treatment effectiveness. Statistically important differences were shown for rs72922019 VAS (week 2), QDASH (weeks 0–4), and PRTEE (week 2); rs12366035 and rs4930152 VAS (week 2), QDASH (week 2), and PRTEE (weeks 2 and 4); and rs594942 and rs595880 VAS (weeks 2 and 4), QDASH (week 2), and PRTEE (weeks 2, 52, and 104). The studied polymorphisms also showed an association with blood morphological parameters, including mean platelet volume, platelet distribution width, and eosinophil levels, as well as some comorbidities (heart failure). Genotyping due to patient selection for therapy may be considered for any of the rs72922019, rs12366035, or rs4930152 polymorphisms.