Although the Challenge-Hindrance Stressor Framework (CHSF) has received considerable attention in work stress research, the role of appraisals has been largely ignored. CHSF assumes that work stressors can be unambiguously divided into challenge and hindrance stressors, suggesting that challenge stressors will be appraised as challenges and hindrance stressors as hindrances. Building on Transactional theory of stress (TTS), our study challenges this assumption by (a) investigating how different work stressors relate to employee appraisals (challenge, hindrance, or threat); (b) testing whether appraisals explain work outcomes beyond work stressors; and (c) identifying the antecedents and outcomes of appraisals. Using 129 samples (N = 38,205), our meta-analysis shows that challenge stressors and hindrance stressors are moderately related to challenge appraisals and hindrance appraisals, respectively. In addition, appraisals account for significant work outcomes beyond stressors. Finally, job resources and personal resources are positively related to employee challenge appraisals, and negatively related to hindrance and threat appraisals. Challenge appraisals are positively related to employee attitudes, motivation, positive emotion, and withdraw behaviors; while hindrance and threat appraisals are positively related to employee strains and withdraw behaviors, and negatively related to employee attitudes and performance. This research contributes to a more nuanced understanding of the CHSF and lays the foundation for future research of work stressor appraisals.