Purpose: Prematurity and low birth weight increase cardiovascular risk, including hypertension (HTN). However, the combined effect of these factors along with others in the development of HTN is unclear. This study aimed to identify changes in blood pressure in small-for-gestational-age (SGA) patients treated with recombinant human growth hormone (rhGH) by comparison with healthy controls. Methods: We conducted a case-control study with 72 SGA and healthy controls, aged 6 to 16 years. Blood pressure was assessed through office and 24-hour ambulatory blood pressure monitoring (ABPM) recordings (at least 40 measurements including daytime and nighttime), and results were compared between SGA children on rhGH treatment and healthy peers. Results: Forty-six SGA children (41% preterm) on rhGH therapy and 26 healthy controls were enrolled. Despite an average of 5 years of rhGH treatment, no significant difference in HTN frequency was found between groups. However, multiple regression analysis revealed a 0.451 increase in 24-hour diastolic blood pressure (DBP) standard deviation score (SDS) in SGA children on rhGH (P=0.032). Daytime DBP SDS was also increased (0.462; P=0.042). An inverse correlation between weight and gestational age at birth was established. SGA children in the prepubertal stage showed a greater increase in 24-hour DBP SDS than those in the pubertal stage (0.499; P=0.009). Overweight was independently associated with increased 24-hour (0.950; P=0.002) and daytime DBP SDS (1.005; P=0.001). Conclusion Prolonged rhGH treatment in SGA patients did not increase the risk of HTN. However, ABPM detected subtle changes that highlight the need for careful blood pressure monitoring in overweight prepubertal children.