This study evaluated various outcomes of home care in a group of 121 chronically ill and frail elderly subjects followed for 24 months, starting from September 2001. The scheduled times of follow up were baseline, 6, 12, and 24 months. Subjects of both sexes were assigned to one of two groups. Control group (CG) (60 subjects: mean age 85.4 years, home care provided by the Social Health Service of the Emilia Romagna Region) and Intervention group (IG) (61 subjects, mean age 82.0 years), for whom the institutional home care was empowered providing a home care attendant. The home care attendant was a person trained in the care of the frail elderly. He/she served from 4 to 24 h daily, according to a program established by a Geriatric Evaluation Unit, considering the needs of the subject and of his/her family members. The cost of the additional home care attendance (HCA) was sponsored (totally or in part), by the "Fondazione del Monte di Bologna e di Ravenna", a non profit foundation. This report takes into consideration the data coming from the first 24 months of follow-up. The two groups were homogenous at baseline. Genetic/molecular pattern including interleukine-1-beta (IL-1b), alfa1-antichimotrypsine (a1ACT), apolipoprotein E4 (APOE4), interleukine-6 (IL-6), tumor necrosis factor-alfa (TNFa), and progression of frailty and disability were considered and discussed. Mortality was lower in the IG than in the CG at 6, 12, and 24 months. Depressive symptoms and disability increased more in IG than in CG; a decrease of the stress of the family members was observed in the IG. The number of drugs used was higher in the CG than in the IG. These outcomes can be related to the additional program of home attendance. The correlation between pro-inflammatory cytokine levels and degree of frailty are observed in both groups without statistically significant difference.