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It is unclear how engaging in physical activity after long periods of inactivity provides expected health benefits.To determine whether physically inactive primary care patients reduce their mortality risk by increasing physical activity, even in low doses.Prospective cohort of 3357 physically inactive patients attending 11 Spanish public primary healthcare centres.Change in physical activity was repeatedly measured during patients' participation in the 'Experimental Program for Physical Activity Promotion' clinical trial between 2003 and 2006, using the '7-day Physical Activity Recall'. Mortality to 31 December 2018 (312 deaths) was recorded from national statistics, and survival time from the end of the clinical trial analysed using proportional hazard models.After 46 191 person-years of follow-up, compared with individuals who remained physically inactive, the mortality rates of those who achieved the minimum recommendations of 150-300 min/week of moderate- or 75-150 min/week of vigorous-intensity exercise was reduced by 45% (adjusted hazard ratio [aHR] 0.55; 95% confidence interval [95% CI] = 0.41 to 0.74); those who did not meet these recommendations but increased physical activity in low doses, that is, 50 min/week of moderate physical activity, showed a 31% reduced mortality (aHR 0.69, 95% CI = 0.51 to 0.93); and, those who surpassed the recommendation saw a 49% reduction in mortality (aHR 0.51, 95% CI = 0.32 to 0.81). The inverse association between increased physical activity and mortality follows a continuous curvilinear dose-response relationship.Physically inactive primary care patients reduced their risk of mortality by increasing physical activity, even in doses below recommended levels. Greater reduction was achieved through meeting physical activity recommendations or adopting levels of physical activity higher than those recommended.