BACKGROUND: The impact of activity-related joint loading on cartilage is not clear. Abnormal loading is considered to be a mechanical driver of osteoarthritis (OA), yet moderate amounts of physical activity and rehabilitation exercise can have positive effects on articular cartilage. Our aim was to investigate the immediate effects of joint loading activities on knee and hip cartilage in healthy adults, as assessed using magnetic resonance imaging. We also investigated delayed effects of activities on healthy cartilage and the effects of activities on cartilage in adults with, or at risk of, OA. We explored the association of sex, age and loading duration with cartilage changes. METHODS: A systematic review of six databases identified studies assessing change in adult hip and knee cartilage using MRI within 48 h before and after application of a joint loading intervention/activity. Studies included adults with healthy cartilage or those with, or at risk of, OA. Joint loading activities included walking, hopping, cycling, weightbearing knee bends and simulated standing within the scanner. Risk of bias was assessed using the Newcastle-Ottawa Scale. Random-effects meta-analysis estimated the percentage change in compartment-specific cartilage thickness or volume and composition (T2 relaxation time) outcomes. The Grading of Recommendations Assessment, Development and Evaluation (GRADE) system evaluated certainty of evidence. RESULTS: Forty studies of 653 participants were included after screening 5159 retrieved studies. Knee cartilage thickness or volume decreased immediately following all loading activities investigating healthy adults; however, GRADE assessment indicated very low certainty evidence. Patellar cartilage thickness and volume reduced 5.0% (95% CI 3.5, 6.4, I2 = 89.3%) after body weight knee bends, and tibial cartilage composition (T2 relaxation time) decreased 5.1% (95% CI 3.7, 6.5, I2 = 0.0%) after simulated standing within the scanner. Hip cartilage data were insufficient for pooling. Secondary outcomes synthesised narratively suggest knee cartilage recovers within 30 min of walking and 90 min of 100 knee bends. We found contrasting effects of simulated standing and walking in adults with, or at risk of, OA. An increase of 10 knee bend repetitions was associated with 2% greater reduction in patellar thickness or volume. CONCLUSION: There is very low certainty evidence that minimal knee cartilage thickness and volume and composition (T2 relaxation time) reductions (0-5%) occur after weightbearing knee bends, simulated standing, walking, hopping/jumping and cycling, and the impact of knee bends may be dose dependent. Our findings provide a framework of cartilage responses to loading in healthy adults which may have utility for clinicians when designing and prescribing rehabilitation programs and providing exercise advice.