The objective of this study was to assess in patients with HIV perceptions of life pre-HIV versus post-HIV diagnosis and examine whether such perceptions change over time. We conducted interviews and chart reviews of 347 outpatients with HIV from three cities in 2002-2004. In two interviews 12-18 months apart, patients compared their life now with their life before HIV was diagnosed. Independent variables included demographic and clinical characteristics; HIV-specific health status, symptoms, and concerns; spirituality/religion; social support; self-perception; and optimism. The patients' mean (standard deviation [SD]) age was 44.8 (8.3) years; half were minorities; and 269 (78%) were taking antiretroviral therapy. Comparing life at time 1 versus before diagnosis, 109 (31%) patients said their life was better at time 1, 98 (28%) said it was worse, and the rest said it was about the same or did not know. By time 2, approximately one fifth of the patients changed their answers to indicate life improvement and one sixth changed them to indicate life deterioration. In multivariable analysis, change in perception for the better between time 1 and time 2 (versus prediagnosis) was positively associated with time 1 positive religious coping scores, whereas change in perception for the worse was associated with study site, heterosexual orientation, a detectable viral load, shorter duration of HIV, lower spirituality scores, and lower positive religious coping scores. We conclude that many patients with HIV feel that their life is better than it was before their diagnosis, although results of such comparisons often change over time.