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Background  Mindfulness Based Stress Reduction (MBSR) is a secular form of meditation training. The vast majority of the extant literature investigating the health effects of mindfulness interventions relies on wait-list control comparisons. Previous studies have found that meditation training over several months is associated with improvements in cognitive control and attention.    Methodology/Principal Findings  We used a visual continuous performance task (CPT) to test the effects of eight weeks of mindfulness training on sustained attention by comparing MBSR to the Health Enhancement Program (HEP), a structurally equivalent, active control condition in a randomized, longitudinal design (ClinicalTrials.gov, NCT01301105) focusing on a non-clinical population typical of MBSR participants. Researchers were blind to group assignment. 63 community participants were randomized to either MBSR (n = 31) or HEP (n = 32). CPT analyses were conducted on 29 MBSR participants and 25 HEP participants. We predicted that MBSR would improve visual discrimination ability and sustained attention over time on the CPT compared to HEP, with more home practice associated with greater improvements. Our hypotheses were not confirmed but we did find some evidence for improved visual discrimination similar to effects in partial replication of other research. Our study had sufficient power to demonstrate that intervention groups do not differ in their improvement over time in sustained attention performance. One of our primary predictions concerning the effects of intervention on attentional fatigue was significant but not interpretable.    Conclusions  Attentional sensitivity is not affected by mindfulness practice as taught in MBSR, but it is unclear whether mindfulness might positively affect another aspect of attention, vigilance. These results also highlight the relevant procedural modifications required by future research to correctly investigate the role of sustained attention in similar samples.    Trial Registration  ClinicalTrials.gov,  NCT01301105

No Sustained Attention Differences in a Longitudinal Randomized Trial Comparing Mindfulness Based Stress Reduction versus Active Control