Fluconazole and dihydropyridine calcium channel blockers (DCCBs) are simultaneously used in clinical practice. Although fluconazole can increase the blood levels of DCCBs by inhibiting CYP3A4, there are only a few reports regarding the effects of interaction of these drugs on blood pressure. Based on electronic medical records, we conducted a retrospective study of blood pressure in hospitalized patients treated with fluconazole while receiving amlodipine and nifedipine. The mean blood pressure over 3 days, specifically 2 days before starting fluconazole treatment and the first day of fluconazole treatment (day 1), was used as the reference value to compare the mean blood pressure calculated every 3 days after day 1 until day 13. Most of the 26 patients included in the study had underlying hematologic malignancies. The average age of patients was 71.8 years. Twenty-one patients received amlodipine and five received nifedipine. The combination of DCCBs and fluconazole was associated with a significant decrease in blood pressure on day 11–13 (p < 0.01). The mean difference in overall systolic blood pressure was −15.8 mmHg (95% CI: −21.1 to −10.4). Therefore, the combination of fluconazole and DCCBs might potentiate the antihypertensive effect of DCCBs, and caution should be exercised when using them for lowering blood pressure.