Objectives To investigate whether tooth loss is associated with increased blood pressure among adults after controlling for socioeconomic, health, and lifestyle confounders. We also assessed the interactions between tooth loss and smoking status and tooth loss and age on systolic blood pressure (SBP). Material and Methods A population-based cross-sectional study was carried out with 1720 adults from Florianõpolis, Brazil. Data collection included blood pressure, anthropometric measures, and a questionnaire on socio-demographics, self-rated health, diabetes, self-reported number of natural teeth, and dental prosthesis. We used linear multivariable regression models for the association of blood pressure with tooth loss adjusting for potential confounders. Results Edentulous subjects had a SBP 8.3 mmHg (95% CI 0.1; 16.7) higher than those with more than 10 teeth in both arches after adjustment for potential confounders. We found interaction between tooth loss and smoking status. Moderate/heavy smokers were associated with considerably higher SBP than light, former or non-smokers among edentulous and also partly among dentate with less than 10 teeth in at least one arch, but there was no real association between smoking and SBP among those with 10 or more teeth in both arches. Conclusions Total tooth loss is associated with increased levels of SBP in this adult population. © 2012 John Wiley & Sons A/S.