Introduction: The association between nocturia and hypertension (HTN) is well-documented. Although recent studies suggest an increased risk of nocturia in patients with treated but uncontrolled hypertension, there is a lack of drug-specific data. With this in mind, we studied the effect of two common antihypertensive agents – hydrochlorothiazide (HCTZ) and angiotensin-converting enzyme inhibitors (Ace-I)/angiotensin II receptor blocker (ARB) – on nocturia in patients with hypertension. Methods: We performed a retrospective analysis of voiding diaries from adult males who were diagnosed with HTN and treated for lower urinary tract symptoms at Brooklyn Veterans Affairs urology clinic. After excluding patients with comorbidities (obstructive sleep apnea, congestive heart failure, chronic kidney disease, diabetes insipidus and mellitus), subjects were divided into four groups: (1) untreated, (2) HCTZ only, (3) Ace-I/ARB only, and (4) HCTZ and Ace-I/ARB. One-way ANOVA with Tukey’s post-hoc test was performed to compare bladder diary parameters and nocturnal urge perception grade (UPG). Results: A total of 234 diaries of adult males with hypertension (mean age ± standard deviation = 69.3 ± 10.4, systolic BP = 129.3 ± 16.6, diastolic BP = 76.1 ± 11.0) were analyzed. Amongst 4 subgroups, hypertensive patients on HCTZ only had the most severe nocturia symptoms with highest actual number of voids (ANV) and nocturia index (Ni) with increased mean nocturnal UPG. This was associated with reduced maximum voided volume (MVV) and increased nocturnal bladder capacity index (NBCi), suggesting diminished bladder capacity in patients on HCTZ only. Interestingly, when Ace-I/ARBs were added to HCTZ, there was a reduction in ANV (p=0.014), NBCi (p=0.001) and UPG (p <0.001). Conclusions: The findings of this study imply that HCTZ worsens nocturia in hypertensive patients likely via diminished nocturnal functional bladder capacity, and addition of ACE Inhibitors/ARBs is associated with reduced nocturia severity. Given that thiazide diuretics and Ace-I/ARBs are frequently prescribed in combination, these results suggest a potential for personalized therapies on treatment of nocturia in patients with hypertension. SOURCE OF Funding: None.