We conducted a study to determine if platelet-rich plasma (PRP) enhances the strength of rotator cuff repair (RCR) and if concomitant use of nonsteroidal anti-inflammatory drugs (NSAIDs) affects PRP efficacy. We also wanted to determine the optimal centrifugation protocol for making PRP from rats. This study used 48 rats, 14 in a centrifugation protocol and 34 in an operative protocol. Six syngeneic rats from the operative group were used as PRP blood donors; the other 28 operative rats underwent bilateral RCRs. The Autologous Conditioned Plasma system (Arthrex) was used to prepare leukocyte-poor PRP. One shoulder was randomized to an intratendinous PRP injection, and the other received normal saline. Each rat was also randomly placed on a postoperative diet, either a regular diet or an indomethacin-enhanced diet. After rats were euthanized at 3 weeks, specimens were dissected to isolate the supraspinatus tendon at its humeral attachment, which was subjected to biomechanical testing. PRP prepared with a protocol of 5 minutes × 1300 revolutions per minute had the highest platelet index. Mean (SD) energy to failure was significantly higher (P = .03) in tendons treated with PRP, 11.7 (7.3) N-mm, than in tendons treated with saline, 8.7 (4.6) N-mm. Both groups (PRP, saline) showed no significant differences between tendons treated with NSAIDs and those not treated with NSAIDs. Intraoperative application of PRP enhances energy to failure after RCR in rats. There were no differences in biomechanical strength with NSAID use and no interactions between PRP and NSAID use.