Background/Aims: There are no published studies assessing the safety and efficacy of thiazides as antihypertensives in kidney transplantation (KTX). Methods: This was a longitudinal retrospective cohort study conducted in adult KTX recipients. Patients were grouped based on receiving thiazides following KTX. Safety and efficacy comparisons were made between thiazide recipients and unexposed patients, as well as change in blood pressure (BP) within thiazide patients. Results: 1,093 patients were included (thiazide group: 108, unexposed group: 985). Mean follow-up was 7.3 ± 4.5 years. Thiazide recipients were older (53 ± 11 vs. 48 ± 13 years, p < 0.001) and more likely to be female (52 vs. 41%, p = 0.023) and have pre-KTX hypertension (97 vs. 88%, p = 0.004) or diabetes (36 vs. 27%, p = 0.035). After controlling for baseline differences, safety analysis revealed thiazide recipients were not more likely to be readmitted to the hospital, but were at higher risk to develop hyperkalemia (56 vs. 38%, p < 0.001) or hypokalemia (28 vs. 18%, p = 0.010), with similar rates of hypotension, decreased estimated glomerular filtration rate, graft loss and death. Efficacy analysis demonstrated systolic (147 ± 17 to 139 ± 18 mm Hg, p < 0.001) and diastolic (79 ± 9 to 77 ± 11 mm Hg, p < 0.001) BPs were significantly reduced after thiazide initiation. Compared to unexposed patients, thiazide recipients had higher mean BPs during the entire follow-up (142/78 vs. 136/77, p < 0.001), with similar BPs while on thiazides and comparable rates of goal BPs (<130/80 mm Hg, 32 vs. 36%, p = 0.219). Conclusions: In KTX, based on long-term outcomes, thiazides appear to be safe and effective antihypertensives; in the short-term, thiazides may increase the risk of developing potassium disturbances.