BACKGROUND: Solid organ transplant (SOT) recipients residing in southwestern United States may be at an increased risk of symptomatic coccidioidomycosis (CM). Accordingly, clinical practice guidelines recommend the use of a universal oral azole antifungal prevention strategy for all SOT recipients residing in a CM endemic area. However, this recommendation is based on limited evidence. Our center does not routinely utilize CM azole antifungal prophylaxis for SOT recipients at low risk for de novo CM infection. OBJECTIVE: To determine the incidence of CM with or without CM prophylaxis in Coccidioides seronegative liver, kidney, and heart transplant recipients residing in endemic areas with no documented history of CM at time of transplant. STUDY DESIGN: A retrospective chart review was performed for SOT recipients who resided in CM endemic areas and received an organ transplant at Keck Hospital of USC between March 2017 and June 2023. Patients receiving CM prophylaxis with fluconazole were compared to patients not receiving CM prophylaxis. The primary end point was incidence of CM infection or asymptomatic seroconversion. RESULTS: In our 85-patient cohort, 18 patients received CM prophylaxis compared to 67 patients who did not. Most patients who received prophylaxis were heart transplant recipients (66.6%). No cases of CM occurred within a median follow-up period of 2.2 years. CONCLUSION: CM prophylaxis can be considered but may not be warranted for liver and kidney transplant recipients residing in Coccidioides endemic areas who are seronegative for Coccidioides and have no history of CM before transplant.