Physical activity (PA) has evidence-based benefits for physical, social and mental health, but investigation of how PA interventions for patients with chronic disease affects their PA practice up to 1 year after programmes are rare. Moreover, few studies document how the context and intervention mechanisms of PA programmes affect sustainable PA practice and its determinants. The present protocol describes a mixed methods study comparing the effectiveness and conditions for the effectiveness of two PA resumption programmes (a hospital-led and a community-based programme). Using a comparative longitudinal study, 60 patients (3-month duration) will be followed for 1 year though four data collections: before (T0) and at the end (T1) of the intervention, 6 months (T2) and 1 year (T3) after the start of the programme. The primary outcome will be PA practice in min/week and categorised as light, moderate or vigorous (using International Physical Activity Questionnaire (IPAQ)), and secondary outcomes will include sedentary time in min/week (IPAQ), quality of life evaluated though the physical and mental composite scores (‘Medical Outcome Study Short Form 12’), and enjoyment using four statements rated from 1 to 5, a high score being synonymous of enjoyment (Intrinsic Motivation Inventory). Qualitative data on further determinants of PA practice and intervention mechanisms will be collected. The expected results will offer the opportunity to understand how the intervention context contributes to a more effective, sustainable PA practice. Trial registration number: NCT04954209 .