BACKGROUND: The authors investigated the effectiveness of conservative (repositioning therapy with or without physical therapy) and helmet therapy, and identified factors associated with treatment failure. METHODS: A total of 4378 patients evaluated for deformational plagiocephaly and/or deformational brachycephaly were assigned to conservative (repositioning therapy, n = 383; repositioning therapy plus physical therapy, n = 2998) or helmet therapy (n = 997). Patients were followed until complete correction (diagonal difference <5 mm and/or cranial ratio <0.85) or 18 months. Rates of correction were calculated, and independent risk factors for failure were identified by multivariate analysis. RESULTS: Complete correction was achieved in 77.1 percent of conservative treatment patients; 15.8 percent required transition to helmet therapy (n = 534), and 7.1 percent ultimately had incomplete correction. Risk factors for failure included poor compliance (relative risk, 2.40; p = 0.009), advanced age (relative risk, 1.20 to 2.08; p = 0.008), prolonged torticollis (relative risk, 1.12 to 1.74; p = 0.002), developmental delay (relative risk, 1.44; p = 0.042), and severity of the initial cranial ratio (relative risk, 1.41 to 1.64; p = 0.044) and diagonal difference (relative risk, 1.31 to 1.48; p = 0.027). Complete correction was achieved in 94.4 percent of patients treated with helmet therapy as first-line therapy and in 96.1 percent of infants who received helmets after failed conservative therapy (p = 0.375). Risk factors for helmet failure included poor compliance (relative risk, 2.42; p = 0.025) and advanced age (relative risk, 1.13 to 3.08; p = 0.011). CONCLUSIONS: Conservative therapy and helmet therapy are effective for positional cranial deformation. Treatment may be guided by patient-specific risk factors. In most infants, delaying helmet therapy for a trial of conservative treatment does not preclude complete correction. CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, III.