In this study, 275 patients in use of tenofovir were retrospectively followed-up for three years to evaluate risk factors involved in impaired renal function. Analysis of variance (ANOVA) and Tukey's test were used to verify any differences in creatinine levels and estimated clearance at 0, 6, 12, 24 and 36 months, adjusting for the co-variables sex, skin color, age >50 years, arterial hypertension, diabetes and the use of the ritonavir-boosted protease inhibitors (PI/r) lopinavir/r or atazanavir/r. The software package STATISTICA 10(®) was used for statistical analysis. The patients' mean age was 43.2±10.7 years. Systemic arterial hypertension (SAH) and diabetes were found in 20.4% and 8.7% of the patients, respectively. Overall, 96.7% were on tenofovir associated with lamivudine (TDF+3TC), 39.3% on lopinavir/r, 29.8% on efavirenz, and 17.6% on atazanavir/r. There was a statistically significant difference in estimated creatinine clearance at 24 months, when the co-variables male (F=3.95; p=0.048), SAH (F=6.964; p=0.009), and age over 50 years (F=45.81; p<0.001) were taken into consideration. Analysis of the co-variable use of atazanavir/r showed a tendency toward an increased risk over time (F=2.437; p=0.063); however, no significant time interaction was seen. At 36-month, a statistically significant difference was found for age over 50 years, (F=32.02; p<0.05) and there was a significant time-by-sex interaction (F=3.117; p=0.0149). TDF was discontinued in 12 patients, one because of a femoral neck fracture (0.7%) and 11 due to nephrotoxicity (4%). Of these latter cases, 9/11 patients were also using protease inhibitors. These data strongly alert that tenofovir use should be individualized with careful attention to renal function especially in male patients, over 50 years, with SAH, and probably those on ATV/r.