Background: Certain social determinants may influence host susceptibility to tuberculosis (TB) infections, and increase the risk of developing the disease. Objectives: The present study aimed to evaluate the effects of several host and environmental factors on the risk of TB in northern Iranian households. Patients and Methods: This case-control study was conducted for one year between 2010 and 2011 in the Guilan province in Iran. Eighty-seven confirmed TB positive cases, based on convenience sampling, were included in this study. A patient positive for TB was confirmed by a positive sputum smear, chest X-ray, and clinical manifestations as diagnosed by a physician. The data were collected using observational methods, and were analyzed by SPSS software. Results: The average mean age of the TB cases was 51 ± 22 years old, and 40.2% (35/87) of the TB cases were male and 59.8% (52/87) were female. The majority of TB cases were from rural areas (71.3%, 62/87), while 28.7% (25/87) were from urban areas. Significant differences (P < 0.001) were observed between the geographical conditions and distribution of the disease. The room density of the individuals was significantly different (2.9 ± 1.2 vs. 2.2 ± 1.9, P < 0.002) among the TB cases and control group, respectively. A statistical difference was observed between the groups in terms of the building materials (P < 0.05), while significantly inadequate UV irradiation was seen in the houses of the TB patients, compared to the control group (82.8% vs. 14.9%, P < 0.001). The hygiene of the houses seemed to be a significant risk factor (P < 0.001) for TB infection. Conclusions: The results suggest that in the studied region several host and environmental factors were associated with higher risks of TB infection.