To determine if mindfulness meditation (MM) in older adults improves cognition and, secondarily, if MM improves mental health and physiology, 134 at least mildly stressed 50–85-year olds were randomized to a 6-week MM intervention or a waitlist control. Outcome measures were assessed at baseline and 2 months later at visit 2. The primary outcome measure was an executive function/attentional measure (flanker task). Other outcome measures included additional cognitive assessments, salivary cortisol, respiratory rate, heart rate variability, Positive and Negative Affect Schedule (PANAS), Center for Epidemiologic Studies Depression (CESD), Perceived Stress Scale (PSS), Neuroticism-Extraversion-Openness (NEO) personality traits, and SF-36 health-related quality of life. One hundred twenty-eight participants completed the study though visit 2 assessments. There was no significant change in the primary or other cognitive outcome measures. Even after statistical adjustment for multiple outcomes, self-rated measures related to negative affect and stress were all significantly improved in the MM intervention compared to waitlist group (PANAS-negative, CESD, PSS, and SF-36 health-related quality of life Vitality and Mental Health Component). The SF-36 Mental Health Component score improved more than the minimum clinically important difference. There were also significant changes in personality traits such as Neuroticism. Changes in positive affect were not observed. There were no group differences in salivary cortisol or heart rate variability. These moderate-sized improvements in self-rated measures were not paralleled by improvements in cognitive function or physiological measures. Potential explanations for this discrepancy in stress-related outcomes are discussed to help improve future studies.