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Objective: To describe the historical, clinical, and diagnostic features of small animal patients affected by cactus‐induced keratoconjunctivitis and their response to therapy. Animals studied: Three dogs and one cat. Procedures: Ophthalmic examination directed subsequent selected diagnostic tests in each case including light microscopy of extracted foreign bodies, in vivo confocal microscopy (IVCM), corneal histopathology, and corneal bacterial culture. Treatments consisted of foreign body surgical extraction with concurrent medical therapy (three cases), or medical therapy alone (one case). Results: Clinical histories obtained supported acute cactus injury in all cases. Ophthalmic abnormalities were unilateral in each case and included ulcerative keratoconjunctivitis associated with linear, microscopic conjunctival and/or corneal penetrating cactus spines, known as glochids. Light microscopy and IVCM showed glochids to be heavily barbed, consistent with the spine morphology Prickly Pear (Opuntia) cactus species. Bacterial culture yielded Proprionicimonas sp. in one case with keratomalacia. Surgical extraction of spines was challenging, and residual conjunctival and/or corneal glochids were present in all cases. Patient discomfort resolved at a median of 21 days (range 10‐51 days). Vision‐threatening complications were not observed in any case at the time of last follow‐up examination. Epithelial downgrowth, demonstrated by IVCM and histopathology, was present in one case at 108‐day follow‐up. Conclusions: Cactus‐induced keratoconjunctivitis should be considered as a differential in regions in which Opuntia cacti are prevalent, and microscopic ocular foreign bodies are observed. Although glochids are difficult to extract, positive clinical outcomes can occur in small animal patients despite the presence of residual organic corneal foreign material. [ABSTRACT FROM AUTHOR]