Background The pathogenesis of tendon overuse injuries is poorly understood. The histopathology underlying tendinopathy at various anatomical locations is similar and may reflect a common pathologic process. Hypothesis Apoptosis contributes to the pathophysiology in patellar tendinopathy. Study Design Case control study; Level of evidence, 3. Methods We compared biopsy specimens from the patellar tendon in patients with patellar tendinopathy diagnosed clinically and with typical magnetic resonance image findings with biopsy specimens from a control group without any previous or current knee complaints to suggest patellar tendinopathy. The presence of apoptosis was examined with immunohistochemical methods using a polyclonal antibody recognizing active caspase-3, confirmed by labeling DNA strand breaks (F7-26 antibody) and nuclear morphology (fragmentation and condensation). Results The number of apoptotic cells per unit area (4.5 mm2) was 0.91 ± 0.81 (SD) in tendinopathic samples and 0.21 ± 0.21 in controls (P = .026). Although the tendinopathic samples displayed increased cellularity (average 162.5 nuclei/mm 2 vs 98.9 nuclei/mm2), the apoptotic index was higher (0.42% vs 0.17%, P = .014). Conclusion Increased apoptotic cell death is a feature of patellar tendinosis. The role of apoptosis within the broader framework and time course of tendon overuse injury remains to be established.