Loneliness is a prevalent social problem with serious physiological and health implications. However, much of the research to date is based on cross-sectional data, including our own earlier finding that loneliness was associated with elevated blood pressure (Hawkley, Masi, Berry & Cacioppo, 2006). In this study, we tested the hypothesis that the effect of loneliness accumulates to produce greater increases in systolic blood pressure (SBP) over a 4-year period than are observed in less lonely individuals. A population-based sample of 229 50- to 68-year-old White, Black, and Hispanic men and women in the Chicago Health, Aging, and Social Relations Study was tested annually for each of 5 consecutive years. Cross-lagged panel analyses revealed that loneliness at study onset predicted increases in SBP 2, 3, and 4 years later (B = 0.152, SE = 0.091, p < .05, one-tailed). These increases were cumulative such that higher initial levels of loneliness were associated with greater increases in SBP over a 4-year period. The effect of loneliness on SBP was independent of age, gender, race or ethnicity, cardiovascular risk factors, medications, health conditions, and the effects of depressive symptoms, social support, perceived stress, and hostility.