Abstract Background despite the well-known adverse health effects of smoking, evidence of these effects on frail individuals is still scarce. Aims to assess whether frailty influences the association between smoking and mortality. Methods individuals ≥50 years from the Mexican Health and Aging Study were analysed. Mortality rates from a 17-year follow-up were compared between smoking status groups (never, previous and current) and other smoking behaviour-related characteristics (pack-years, age commenced and cessation). Baseline variables were included to adjust the Cox regression models. First, models were adjusted for the whole sample, including an interaction term between the frailty index (FI) and smoking variables. A second set of models were stratified by FI levels: 0.00–0.10, 0.11–0.20, 0.21–0.30 and ≥ 0.31. Results from a total 14,025 individuals, mean age was 62.4 (95% confidence interval [95% CI]: 62.1–62.8) and 53.9% were women (95% CI: 52.4–55.6). Main results from the survival analyses showed that when including FI interaction term with smoking status, comparing current to never smoking, the hazard ratio (HR) was 2.03 (95% CI: 1.07–3.85, P = 0.029), and comparing current to previous smoking, the HR was 2.13 (95% CI: 1.06–4.26, P = 0.032). Models stratified by FI levels showed a significant HR only for the two highest level groups. Similar results were found for the smoking behaviour-related characteristics. Discussion our results suggest that frailty could modify smoking mortality risk. Other smoking characteristics were impacted by frailty, in particular, cessation. It was noteworthy that having ≥10 years of tobacco cessation was beneficial for frail individuals. Conclusions smoking has a higher toll on frail individuals, but ceasing is still beneficial for this group.