Rationale: Natural history of preserved ratio impaired spirometry (PRISm), often defined as FEV1/FVC ≥lower limit of normal and FEV1 <80% of predicted value, is not well described. Objectives: To investigate the natural history and long-term prognosis of the following PRISm trajectories: persistent PRISm trajectory (individuals with PRISm both young and middle-aged), normal to PRISm trajectory (individuals developing PRISm from normal spirometry in young adulthood), and PRISm to normal trajectory (individuals recovering from PRISm in young adulthood by normalizing spirometry while middle-aged). Methods: We followed 1,160 individuals aged 20-40 years fromthe Copenhagen City Heart Study from 1976 to 1983 until 2001 to 2003 to determine their lung function trajectory; 72 had persistent PRISm trajectory, 76 had normal to PRISmtrajectory, 155 had PRISmto normal trajectory, and 857 had normal trajectory. From2001-2003 until 2018, we determined the risk of cardiopulmonary disease and death. Measurements and Main Results: We recorded 198 admissions for heart disease, 143 for pneumonia, and 64 for chronic obstructive pulmonary disease as well as 171 deaths. Compared with individuals with normal trajectory, hazard ratios for individuals with persistent PRISm trajectory were 1.55 (95% confidence interval, 0.91-2.65) for heart disease admission, 2.86 (1.70-4.83) for pneumonia admission, 6.57 (3.41-12.66) for chronic obstructive pulmonary disease admission, and 3.68 (2.38-5.68) for all-cause mortality. Corresponding hazard ratios for individuals with normal to PRISm trajectory were 1.91 (1.24-2.95), 2.74 (1.70-4.42), 7.61 (4.21-13.72), and 2.96 (1.94-4.51), respectively. Prognosis of individuals with PRISm to normal trajectory did not differ from those with normal trajectory. Conclusions: PRISm in middle-aged individuals is associated with increased risk of cardiopulmonary disease and all-cause mortality, but individuals who recover from PRISm during their adult life are no longer at increased risk.