To determine whether higher physical activity after prostate cancer (PCa) diagnosis decreases risk of overall and PCa-specific death. We evaluated physical activity in relation to overall and PCa mortality among 2,705 men in the Health Professionals Follow-Up Study diagnosed with nonmetastatic PCa observed from 1990 to 2008. Proportional hazards models were used to evaluate physical activity and time to overall and PCa-specific death. Among men who lived at least 4 years after their postdiagnosis physical activity assessment, we documented 548 deaths, 20% of which were a result of PCa. In multivariable analysis, men who were physically active had lower risk of all-cause mortality (P(trend) < .001) and PCa mortality (P(trend) = .04). Both nonvigorous activity and vigorous activity were associated with significantly lower overall mortality. Those who walked ≥ 90 minutes per week at a normal to very brisk pace had a 46% lower risk of all-cause mortality (hazard ratio [HR] 0.54; 95% CI, 0.41 to 0.71) compared with shorter durations at an easy walking pace. Men with ≥ 3 hours per week of vigorous activity had a 49% lower risk of all-cause mortality (HR, 0.51; 95% CI, 0.36 to 0.72). For PCa-specific mortality, brisk walking at longer durations was suggestively inverse but not statistically significant. Men with ≥ 3 hours per week of vigorous activity had a 61% lower risk of PCa death (HR, 0.39, 95% CI, 0.18 to 0.84; P = .03) compared with men with less than 1 hour per week of vigorous activity. Men exercising vigorously before and after diagnosis had the lowest risk. In men with PCa, physical activity was associated with lower overall mortality and PCa mortality. A modest amount of vigorous activity such as biking, tennis, jogging, or swimming for ≥ 3 hours a week may substantially improve PCa-specific survival.