Given the complications involved in corticosteroid (CS) injections, subacromial platelet-rich plasma (PRP) injections may provide a valid alternative to CS in the treatment of rotator cuff (RC) tendinopathy. Methods: We retrospectively reviewed a total of 98 patients affected by RC tendinopathy who were treated with either subacromial injection of PRP or CS. The PRP group received three injections of autologous PRP at 2 weeks interval, and the CS group received one injection of CS. The Western Ontario Rotator Cuff Index (WORC) was the primary outcome measure, while the secondary outcome measures were the visual analog scale (VAS), range of motion (ROM), and need for cuff repair surgery, which were analyzed at intervals of 6, 12, and 18 months. Results: A total of 75 patients were included in the analysis (PRP, n=35; CS, n=40). The mean follow-up for PRP was 21.1±8.7 months and for CS was 33.6±16.3 months (p<0.001). Both groups showed improvement in WORC, VAS, and ROM. No significant differences were detected between the two groups in any of the primary (WORC) or secondary outcomes over 6, 12, and 18 months (all p>0.05). No adverse events were detected. Conclusions: Both treatments improved patient symptoms, but neither resulted in a significantly better outcome in this series of patients. PRP can be a safe and feasible alternative to CS, even at long-term follow-up, to reduce local and systemic effects involved with CS injections.