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This research study sought to answer if one's religious belief can influence the effect of a Buddhist mind-body intervention in a specific patient population. Individuals with tension headaches were categorized according to religious belief, Christian (conservative vs. liberal), Non-Christian and Other. Two research questions were examined: (1) Is there differences in spiritual practices and religious belief over time between the intervention and comparison groups and (2) Is there differences in salivary immunoglobulin A (sIgA) and religious belief over time between groups? A mixed pre-/post-experimental design with pre-/post-longitudinal measurements was used to examine this question. The sample consisted of 50 women and 14 men with tension headaches, aged 18–70; 34 were randomly assigned to an intervention group and 30 to a comparison group. Intervention participants received an 8-week Buddhist mindfulness meditation class, 2 hours a week. Comparison participants received an 8-week educational class in headaches, 1˝ hours a week. Pre- and post-testing measurements were obtained on spiritual practices and sIgA. Analysis results, using univariate repeated measures ANOVAs indicated (1) a statistically significant mean difference for spiritual practices by religious belief at post-test and (2) a statistically significant mean difference for the dependent variable of sIgA by religious belief at post-test with the intervention group to have a higher post-treatment sIgA level than the comparison group. Within the intervention group the liberal Christians and non-Christians had a greater increase in sIgA than conservative Christians. Conservative Christians were unable to experience the immune enhancing effect of a Buddhist mindfulness intervention. This research study validated the necessity of spiritual congruence.