IntroductionWith declining HIV-related mortality, over 20% of people with HIV (PWH) in South Africa are now over age 50 years, and tobacco-related non-communicable disease burden is increasing. We quantified the impact of smoking and smoking cessation on lung cancer and stroke incidence among PWH in South Africa.MethodsUsing a microsimulation model, we simulated 18 cohorts of initially virologically suppressed PWH over their lifetime, categorised by sex, initial age (35 years/45 years/55 years) and smoking status (current/former/never). Smoking status remains constant throughout the simulation; individuals with former smoking status quit at model start. PWH can disengage from HIV care and experience virological rebound. We modelled the relative risk of lung cancer for females (males) with current versus never smoking status as 16.69 (15.83), and for females (males) with former versus never smoking status as 1.99–8.80 (1.90–6.18), depending on age at cessation. Corresponding modelled relative risks of stroke were 1.79 (1.54) for current versus never smoking, and 1.00–1.29 (1.00–1.12) for former versus never smoking. We varied HIV-related and smoking-related parameters in sensitivity analyses.ResultsModelled female (male) PWH who stop smoking at age 45 years experience 61.3% (70.9%) and 35.6% (18.6%) lower cumulative lung cancer and stroke incidence over 25 years compared with people who continue smoking. The proportion alive and lung cancer-free or alive and stroke-free over 25 years would increase by 10.4 (9.5) or 10.5 (8.5) percentage points. In sensitivity analysis, smoking and smoking cessation have a greater impact on lung cancer and stroke cumulative incidence if competing HIV-related mortality risks are lower or if PWH experience higher lung cancer and stroke risk compared with people without HIV apart from smoking.ConclusionSmoking cessation could substantially reduce lung cancer and stroke risk among PWH in South Africa. To reduce the rising non-communicable disease burden among PWH, smoking cessation should become part of routine care of PWH.