BACKGROUND: Occupations might influence the employees’ psychophysical conditions and an important issue is the human activity mechanization, which favors a hypokinetic work status and leads to several chronic diseases. One of the most hypokinetic occupations is the supermarket cashier, in which the individual may spend many hours a day in the same body position. OBJECTIVE: The goal of this study was to evaluate the association between cardiovascular risk, quality of life and physical activity level in supermarket cashiers. METHODS: This is a cross-sectional study which included 200 supermarket cashiers aged 20 to 41 years from São Paulo, Brazil. The following cardiovascular risk factors were evaluated: overweight, obesity, hypertension, diabetes mellitus, and tobacco smoking. Physical activity level and quality of life were assessed with the short-form of the International Physical Activity Questionnaire (IPAq) and World Health Organization Quality of Life (WHOQOL), respectively. Student t test and Chi-square were carried out to evaluate mean gender comparations and frequency, respectively. Logistic regression models were applied to determine the association between cardiovascular risk factors and physical activity level. RESULTS: The prevalence for all cardiovascular risk factors was significantly high in the cashiers with a low physical activity level. However, there was a significant reduction in several risk factors in the groups with moderate and high physical activity levels. The odds ratio values were significantly reduced for the association between the cardiovascular risk factors and the moderate and high physical activity levels. The cashiers with moderate and high physical activity levels showed significantly higher quality of life scores for the social and environmental domain. CONCLUSIONS: A high physical activity level is positively related to quality of life in supermarket cashiers.