Hypertension (HT) is diagnosed with high office blood pressure (BP), although confirmation with the addition of out-of-office measurements is currently recommended. However, insufficient data are available concerning the use of out-of-office BP measurement techniques for the diagnosis of HT in the prehypertensive population. The aim of the present study was to determine which out-of-office measurements yielded earlier and more frequent detection of development of HT in prehypertensive patients. Two hundred seven prehypertensive patients under monitoring in the Cappadocia cohort were included in the study. Office BP was measured five times at 1-min intervals, followed by 24-h ambulatory BP monitoring (24-h ABPM). Home BP measurement (HBPM) was performed five times, at the same times in the morning and evening, at 1-min intervals for 1 week. The same procedure was carried out at 4-6-month intervals for ~2 years. HT was diagnosed in 25.6% of subjects, masked HT in 11.1%, and white coat HT in 2.9%, while 23.7% remained prehypertensive and 36.7% became normotensive. Briefly, 56.6% of the patients with HT were diagnosed with office plus 24-h ABPM, 13.2% with office plus HBPM, and 30.2% with office plus HBPM and 24-h ABPM. Office with 24-h ABPM yielded statistically significantly more diagnoses (p < 0.001). In conclusion, our prospective observational study evaluated the usefulness of out-of-office BP measurements in confirming diagnosis of HT in prehypertensive patients. The findings show that 24-h ABPM detected HT earlier and more frequently in this high-risk population.