Objective To analyze the risk factors of fluconazole resistance in Candida tropicalis (C. tropicalis) urinary tract infection (UTI), and evaluate the efficacy of different treatment regimens. Methods Patients with C. tropicalis UTI at Xiangya Hospital of Central South University from January 2021 to December 2023 were included for single center retrospective study. The minimum inhibitory concentration (MIC) of fluconazole was determined by microbroth dilution. Patients were divided into a fluconazole-resistant group and a fluconazole-sensitive group based on fluconazole resistance. Risk factors for fluconazole resistance were analyzed based on clinical data, and therapeutic efficacy in patients in fluconazole-resistant group was analyzed. Results A total of 198 patients were included in the study. 133 (67.2%) C. tropicalis strains were detected to be sensitive to fluconazole, while 65 (32.8%) strains were resistant, and 63.1% (n=41) had MIC values ≥128 μg/mL. Compared with fluconazole-sensitive group, fluconazole-resistant group had a higher proportion of pulmonary infection (P=0.019). Pulmonary infection (OR=3.282) was a risk factor for fluconazole resistance in C. tropicalis UTI, while urinary system obstruction (OR=0.269) was a protective factor for fluconazole resistance in C. tropicalis UTI. There was no statistically significant difference in the usage rate of different antimicrobial agent types between the two groups (all P>0.05). The therapeutic efficacy analysis showed that the effective rates of treatment with fluconazole dosage regimens of ≤200 mg/d, ≥400 mg/d, and fluconazole monotherapy against fluconazole-resistant strains were 66.7% (6/9), 83.3% (5/6), and 100% (6/6), respectively. For patients treated with monotherapy using other drugs or with multidrug sequential treatment regimens, the treatment effective rate was 60.0% (3/5). The proportion of patients in the effective treatment group who removed their urinary catheters after detecting C. tropicalis was higher than that in the ineffective treatment group (P<0.001). Conclusion The fluconazole resistance of C. tropicalis is related to urinary tract obstruction and concurrent pulmonary infection. When treating UTI caused by fluconazole-resistant strains, the catheter should be removed as early as possible. In addition to increasing the dosage of fluconazole, other antifungal drugs such as flucytosine alone or sequential treatment with multiple drugs can also be considered.