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This paper examined early developmental trajectories in a large, longitudinal sample at high-risk for ASD (‘HR’) and low-risk (‘LR’) controls, and the association of trajectories with 3-year diagnosis. Developmental assessments were conducted at 6, 12, 24 months, and 3 years, with blinded “clinical best-estimate” expert diagnosis at age 3. HR infants were enrolled based only on familial risk. LR infants, from community sources, had no first- or second-degree ASD relatives. All infants were born at 36–42 weeks, weighing ≥2500 g, with no identifiable neurological, genetic, or severe sensory/motor disorders. Analytic phase I: semi-parametric group-based modeling to identify distinct developmental trajectories ( n = 680; 487 HR; 193 LR); phase II: Trajectory membership in relation to 3-year diagnosis ( n = 424; 310 HR; 114 LR). Three distinct trajectories emerged (1) inclining; (2) stable-average; (3) declining; trajectory membership predicted diagnosis ( χ 2 = 99.40; p < .001). Most ASD cases were in stable-average (50.6%) or declining trajectories (33.8%); most non-ASD-HR infants were in inclining (51.9%) or stable-average (40.3%) trajectories. The majority of LR controls were in the inclining trajectory (78.9%). Within the declining trajectory, over half had ASD (57.8%), but 40% were non-ASD-HR infants. Declining/plateauing raw scores were associated with, but not exclusive to, ASD. Findings underscore the importance of monitoring the emergence of ASD symptoms and overall development in high-risk children. Evidence of developmental slowing or decline may be associated not only with ASD, but with other suboptimal outcomes, warranting careful clinical follow-up. [ABSTRACT FROM AUTHOR]