Prospective studies show that high C-reactive protein (CRP) levels predict diabetes and cardiovascular disease (CVD), but changes in this marker preceding disease onset are not well characterized. This study describes CRP trajectories prior to type 2 diabetes onset and fatal CVD. In a prospective cohort of 7350 British civil servants (70% male, mean age 51 years), 558 incident type 2 diabetes cases (75-g oral glucose tolerance test, doctor's diagnosis, or self-report) and 125 certified fatal cardiovascular events were observed during a median follow-up of >14 years. Trajectories of logarithmically transformed CRP levels prior to incident diabetes or fatal cardiovascular event (cases), or the end of follow-up (controls) were calculated using multilevel modeling. Baseline CRP levels were higher among participants who developed diabetes (median (interquartile range) 1.44 (2.39) vs 0.78 (1.21) mg/l) or fatal CVD (1.49 (2.47) vs 0.84 (1.30) mg/l) compared with controls (both P<0.0001). In models adjusted for age, sex, body mass index, ethnicity, and employment grade, CRP levels increased with time among both incident diabetes cases and controls (P<0.0001), but this increase was less steep for cases group (P<0.05). CRP levels followed increasing linear trajectories in fatal cardiovascular cases and controls (P<0.0001) with no slope difference between the groups. CRP levels were higher among those who subsequently developed diabetes or died from CVD. For type 2 diabetes, age-related increase in CRP levels was less steep in the cases group than in controls, whereas for fatal CVD these trajectories were parallel.