Although increasing age is often thought to be associated with slower oxidative drug clearance, limited data from old, very old, and frail patients exist. Our objective was to determine the effects of very old age and frailty on erythromycin breath test (ERBT) results in patients and, secondarily, to determine the effects of sex and comedications on ERBT results.ERBTs were performed in 60 individuals aged 65 to 101 years, 27 of whom were classified as frail (mean age [+/-SD], 86 +/- 6 years; mean weight, 66 +/- 17.4 kg; 8 men and 19 women; 24 living in a nursing home and 3 living in the community) and 33 of whom were classified as nonfrail (mean age, 79 +/- 8 years; mean weight, 78.5 +/- 14.5 kg; 16 men and 17 women; 17 living in a nursing home and 16 living in the community).ERBT results were faster in women versus men (3.53% +/- 1.15% carbon 14 [14C] excreted/h versus 2.59% +/- 0.99% 14C excreted/h, respectively; ANOVA, P < .002), faster in frail versus nonfrail patients (3.58% +/- 1.2% 14C excreted/h versus 2.81% +/- 1.06% (14)C excreted/h, respectively; ANOVA, P = .01), and faster in those receiving cytochrome P450 (CYP) 3A inducers versus those without inducers (5.02% +/- 0.89% 14C excreted/h versus 3.02% +/- 1.08% 14C excreted/h, respectively; ANOVA, P = .0007). When subjects receiving CYP inducers were excluded, sex affected ERBT results (ANOVA, P < .007) but frailty effects were not detected (P = .09). Age from 65 to 101 years did not affect ERBT results (r2 = 0.001).Old and very old patients in the clinical setting, especially women and those receiving enzyme inducers, may have preserved medication clearance. Frail elderly persons do not have slower ERBT results compared with nonfrail elderly persons.