Low birth weight and unhealthy lifestyle are both associated with an increased risk of hypertension. The authors aimed to assess the joint association and interaction of birth weight and lifestyle with incident hypertension. The authors included 205522 participants free of hypertension at baseline from UK Biobank. A healthy lifestyle score was constructed using information on body mass index, physical activity, diet, smoking status and alcohol intake. Cox proportional hazard models were used to investigate the impact of birth weight, healthy lifestyle score and their joint effect on hypertension. The authors documented 13548 (6.59%) incident hypertension cases during a median of 8.6years of follow-up. The multivariate adjusted hazard ratios and 95% confidence intervals were 1.12 (1.09, 1.15) per kg lower birth weight and 0.76 (0.75, 0.77) per score increment in healthy lifestyle score. Healthy lifestyle reduced the risk of hypertension in any category of different birth weight groups. The preventive effect of healthy lifestyle on hypertension was the most pronounced at lower birth weight with <2500g and 2500-2999g, respectively. Addictive interaction between birth weight and healthy lifestyle score was observed with the relative excess risk due to interaction of 0.04 (0.03, 0.05). Our findings emphasized the importance of healthy lifestyle for hypertension prevention, especially among the high-risk population with lower birth weight.