A single clinic measurement of blood pressure (BP) may be common in low- and middle-income countries because of limited medical resources. This study aimed to examine the potential misclassification error when only one BP measurement is used. Participants (n = 14,706, 53.5% females) aged 25–64 years were selected by multistage stratified cluster sampling from eight provinces, each representing one of the eight geographical regions of Vietnam. Measurements were made using the World Health Organization STEPS protocols. Data were analyzed using complex survey methods. For systolic BP, 62.7% had a higher first reading whereas 30.0% had a lower first reading, and 27.3% had a reduction of at least 5 mmHg whereas 9.6% had an increase of at least 5 mmHg. Irrespective of direction of change, increased variability in BP was associated with greater age, urban living, greater body size and fatness, reduced physical activity levels, elevated glucose, and raised total cholesterol. These measurement variations would lead to substantial misclassification in diagnosis of hypertension based on a single reading because almost 20% of subjects would receive a different diagnosis based on the mean of two readings.