Objectives: While psychosocial stress and high effort coping have been associated with reduced immune function, no epidemiologic study has addressed psychological stress and risk of prostate cancer. The purpose of this analysis was to investigate the association between stress, coping, social support, and risk of prostate cancer among older men (age 65–79 years). Design: Population-based case-control study in South Carolina. Participants: Cases were 400 incident, histologically confirmed prostate cancer cases identified through the South Carolina Central Cancer Registry between 1999 and 2001 (70.6% response rate). Controls were 385 men identified through the 1999 Health Care Financing Administration Medicare beneficiary file for South Carolina (63.8% response rate). Main Outcome Measures: Consenting participants completed telephone interviews addressing demographics (age, race, income, education, marital status, body mass index), medical and prostate cancer screening history, stress (Global Perceived Stress), coping (John Henryism Scale), and social support. Results: After adjusting for age, race, and South Carolina region, higher John Henryism scores (.24) were modestly associated with prostate cancer risk relative to lower scores (,24) (adjusted odds ratio 1.63, 95% confidence interval 1.11–2.40). This effect is somewhat more pronounced among those perceiving some stress, yet the effect of John Henryism on prostate cancer risk was reduced among those with high levels of social support. Neither higher stress nor social support alone was associated with prostate cancer risk. Conclusions: Higher John Henryism scores indicating high-effort coping may be associated with an increase in prostate cancer risk.