BACKGROUND Uncertainty still exists whether physical activity (PA) and cardiovascular fitness (CF) contribute separately to cardiovascular disease (CVD) risk. This study examined the associations of PA and CF on individual as well as clustered CVD risk factors. METHODS Cross-sectional. METHODS Seven hundred and eighty-one men and 890 women, aged 20-65 years, from two random population-based samples of Swedish women and men were included. PA was assessed by questionnaire and CF was predicted by a submaximal cycle ergometry test. Waist circumference, blood pressure, and fasting levels of blood lipids were assessed and dichotomized by conventional cut-off points. RESULTS Participants reporting high PA level benefited from lower triglycerides and atherogenic cholesterol levels, regardless of CF. Higher CF level was, regardless of PA, associated with lower risk for all risk factors. With regard to clustering of risk factors, each higher CF level was associated with a gradually reduced risk by half or more, independent of PA. Furthermore, being unfit but reporting high PA was associated with a 50% lower risk compared with being unfit and inactive. Furthermore, high reported PA was associated with an additional reduced risk among fit participants. In addition, an excess risk of interaction was found for waist circumference, triglycerides, and the clustered CVD risk between neither being sufficiently active nor being fit. CONCLUSIONS This study suggests that both PA and CF are independently associated with lower cardiovascular risk, and that both variables should be taken into account when CVD risk is estimated.