OBJECTIVE The aim of this study was to assess the effect of religious attendance and spirituality on the relationship between negative life events and psychological distress. METHODS This was a cross-sectional study of 1,071 community dwelling adults from East Baltimore, Maryland who participated in the fourth (2004-2005) wave of the Baltimore Epidemiologic Catchment Area study. The 20-item General Health Questionnaire (GHQ-20) was used to measure psychological distress. Multiple regression models were used to assess the association between negative life events and distress as well as to measure the effect of religious attendance and spirituality on the association between psychological distress and negative events while adjusting for demographic variables, past distress and social support from friends and relatives. RESULTS In pooled analysis, negative events were significant predictors of distress, b = 1.00, β = 0.072, p < 0.05. Religious attendance and spirituality did not affect or modify the association between negative events and distress. However, religious attendance was inversely associated with distress with higher frequency of attendance associated with lower distress after controlling for demographic and social support factors, b = -2.10, β = -.110, p < 0.01 for attending 1-3 times a month; b = -2.39, β = -0.156, p < 0.01 for attending weekly; and b = -3.13, β = -0.160, p < 0.001 for attending more than once per week. In stratified analysis, negative events were associated with distress for those who were low on spirituality, b = 1.23, β = 0.092, p < .05, but not for those who were high on spirituality; the association between religious attendance and decreased distress was true only for those scoring high in spirituality. Social support accounted for some of the inverse association between religious and distress. CONCLUSIONS Religious attendance and spirituality may play a role in how people experience and deal with difficult life situations.