BACKGROUND Rotator cuff tear (RCT) is a frequent condition of clinical relevance that can be managed with a symptomatic conservative treatment, but surgery is often needed. Biological components like leukocytes and platelet rich plasma (L-PRP) could represent an alternative curative method for interstitial RCT. HYPOTHESES It has been hypothesized that an ultrasound guided L-PRP injection in supraspinatus interstitial RCT could induce radiological healing. MATERIAL AND METHODS A prospective case series including 25 patients was performed in order to assess the effect of L-PRP infiltration into supraspinatus interstitial RCTs. Primary outcome was tear size change determined by magnetic resonance imaging arthrogram (MRA) before and 6 months after L-PRP infiltration. Secondary outcomes were Constant score, SANE score, and pain visual analog scale (VAS) after L-PRP infiltration. RESULTS Tear volume diminution was statistically significant (P=.007), and a >50% tear volume diminution was observed in 15 patients. A statistically significant improvement of Constant score (P<.001), SANE score (P=.001), and VAS (P<.001) was observed. In 21 patients, Constant score improvement reached the minimal clinical important difference of 10.4 points. DISCUSSION We observed a statistically significant and clinically relevant effect on RCT size and clinical parameters after L-PRP infiltration. Such an important improvement of supraspinatus interstitial RCT with conservative management is uncommon, therefore intratendinous L-PRP infiltrations could have been beneficial. This encouraging result could pave the way for future randomized studies in order to formally determinate whether L-PRP infiltrations are a possible alternative to surgical treatment of interstitial RCT. LEVEL OF EVIDENCE Prospective observational study; Level of evidence II.