A rest period of 3 to 5 minutes before blood pressure (BP) measurement is recommended in hypertension guidelines but can be challenging to implement. We conducted a randomized trial to determine the effects of resting for <5 minutes on BP. In a cross-over design, 113 participants (mean age 55 years, 36% male, 75% Black) had 4 sets of triplicate BP measurements with the order of rest for the first 3 sets (0 minutes, 2 minutes, 5 minutes1) randomized. The fourth set was always a second 5-minute rest period (5 minutes2), from which we calculated the difference between 5 minutes1 and 5 minutes2 (5 minutes1−5 minutes2), a measure of intrinsic BP variability. To determine if there was no difference between BPs obtained after resting 0 minutes or 2 minutes versus 5 minutes1, we tested whether 5 minutes1−0 minutes or 5 minutes1−2 minutes was within a prespecified noninferiority margin of ±2 mm Hg compared with 5 minutes1−5 minutes2. Overall, mean BP was similar across 5 minutes1 (128/75), 5 minutes2 (127/76), 2 minutes (127/74), and 0 minutes (127/74). Compared with the average absolute 5 minutes1−5 minutes2 difference (5.3/3.0 mm Hg), the absolute systolic BP difference of differences did not cross our noninferiority margin for 0 minutes rest (0.2 [95% CI, 0.8–1.2]) but did for 2 minutes rest (−1.7 [−2.8 to −0.6]). Among those with systolic BP <140, the absolute difference of differences for both 0 and 2 minutes did not cross the ±2 mm Hg margin; however, those with systolic BP ≥140 had differences that did exceed this threshold. Our findings suggest that shorter rest periods may be a reasonable alternative to 5 minutes for most individuals. Implementation could substantially improve the efficiency of hypertension screening programs.