Aims: Leisure time physical activity associates with reduced risk of cardiovascular disease and all-cause mortality, while these relationships for occupational physical activity are unclear. We tested the hypothesis that leisure time physical activity associates with reduced major adverse cardiovascular events (MACE) and all-cause mortality risk, while occupational physical activity associates with increased risks. Methods and results: We studied 104 046 women and men aged 20-100 years in the Copenhagen General Population Study with baseline measurements in 2003-2014 and median 10-year follow-up. Both leisure and occupational physical activity were based on self-report with four response categories. We observed 7913 (7.6%) MACE and 9846 (9.5%) deaths from all causes. Compared to low leisure time physical activity, multivariable adjusted (for lifestyle, health, living conditions, and socioeconomic factors) hazard ratios for MACE were 0.86 (0.78-0.96) for moderate, 0.77 (0.69-0.86) for high, and 0.85 (0.73-0.98) for very high activity; corresponding values for higher occupational physical activity were 1.04 (0.95-1.14), 1.15 (1.04-1.28), and 1.35 (1.14-1.59), respectively. For all-cause mortality, corresponding hazard ratios for higher leisure time physical activity were 0.74 (0.68-0.81), 0.59 (0.54-0.64), and 0.60 (0.52-0.69), and for higher occupational physical activity 1.06 (0.96-1.16), 1.13 (1.01-1.27), and 1.27 (1.05-1.54), respectively. Similar results were found within strata on lifestyle, health, living conditions, and socioeconomic factors, and when excluding individuals dying within the first 5 years of follow-up. Levels of the two domains of physical activity did not interact on risk of MACE (P = 0.40) or all-cause mortality (P = 0.31). Conclusion: Higher leisure time physical activity associates with reduced MACE and all-cause mortality risk, while higher occupational physical activity associates with increased risks, independent of each other.