Longitudinal strain (LS) has been shown to be predictive of outcome in hypertrophic cardiomyopathy (HC). Percent predicted peak oxygen uptake (ppVO₂), among other cardiopulmonary exercise testing (CPX) metrics, is a strong predictor of prognosis in HC. However, there has been limited investigation into the combination of LS and CPX metrics. This study sought to determine how LS and parameters of exercise performance contribute to prognosis in HC. One hundred and thirty-one consecutive patients with HC who underwent CPX and stress echocardiography were included. Global, septal, and lateral LS were assessed at rest and stress. Eighty matched individuals were used as controls. Patients were followed for the composite end point of death and worsening heart failure. All absolute LS components were lower in patients with HC than in controls (global 14.3 ± 4.0% vs 18.8 ± 2.2%, p <0.001; septal 11.9 ± 4.9% vs 17.9 ± 2.7%, p <0.001; lateral 16.0 ± 4.7% vs 19.4 ± 3.1%, p = 0.001). Global strain reserve was also reduced in patients with HC (13 ± 5% vs 19 ± 8%, p = 0.002). Over a median follow-up of 56 months (interquartile range 14 to 69), the composite end point occurred in 53 patients. Global LS was predictive of outcome on univariate analysis (0.55 [0.41 to 0.74], p <0.001). When combined with CPX metrics, lateral LS was the only strain variable predictive of outcome along with indexed left atrial volume (LAVI) and ppVO₂. The worst outcomes were observed for patients with lateral LS <16.1%, LAVI >52 ml/m², and ppVO₂ <80%. The combination of lateral LS, LAVI, and ppVO₂ presents a simple model for outcome prediction.