Introduction Family caregivers of patients with heart failure (HF) commonly experience emotional distress and caregiving burden. Despite their caregiving distress, caregivers may experience positive or negative changes in their life compared with before caregiving. Greater perceived control is associated with better health outcomes, but little is known about whether perceived control is related to caregivers perceptions of positive or negative changes in life, independent of their distress and burden in providing care for patients with HF. The specific aims were to compare emotional distress and caregiving burden between caregivers who perceived positive versus negative changes in life due to caregiving and to examine whether perceived control predicts the perception of positive or negative changes in life while controlling for emotional distress and caregiving burden. Methods Primary caregivers of patients with HF (N = 140, 75% women) completed questionnaires about perceived positive or negative changes in life as a result of caregiving, perceived control, depressive symptoms, anxiety, and caregiving burden. Independent t test, chi(2), and logistic regressions were used to accomplish specific aims. Results Compared with caregivers who reported positive changes in life (42%), caregivers who perceived negative changes in life (58%) had higher levels of depressive symptoms, anxiety, and caregiving burden. Lower level of perceived control was an independent predictor of perceived negative changes in life, controlling for age, gender, depressive symptoms, anxiety, and caregiving burden (odds ratio, 0.89; 95% confidence interval, 0.79-0.99; P = .0038). Conclusion Greater perceived control played a protective role for caregivers independent of caregiver burden. Interventions designed to enhance perceived control may improve caregivers perceptions of changes in their life.