Guided by the extended parallel process model (EPPM) and reactance theory, this study examined the relationship between efficacy beliefs, reactance, and adult smokers' responses to pictorial health warning labels (HWL) on cigarette packaging, including whether efficacy beliefs or reactance modify the relationship between HWL responses and subsequent smoking cessation behavior. Four waves of data were analyzed from prospective cohorts of smokers in Australia and Canada (n = 7,120 observations) over a period of time after implementation of more prominent, pictorial HWLs. Three types of HWL responses were studied: psychological threat responses (i.e., thinking about risks from smoking), forgoing cigarettes due to HWLs, and avoiding HWLs. The results from Generalized Estimating Equation models indicated that stronger efficacy beliefs and lower trait reactance were significantly associated with greater psychological threat responses to HWLs. Similar results were found for models predicting forgoing behavior, although response efficacy was inversely associated with it. Only response efficacy was significantly associated with avoiding HWLs, showing a positive relationship. Higher self-efficacy and stronger responses to HWLs, no matter the type, were associated with attempting to quit in the follow-up period; reactance was unassociated. No statistically significant interactions were found. These results suggest that stronger efficacy beliefs and lower trait reactance are associated with some stronger responses to fear-arousing HWL responses; however, these HWL responses appear no less likely to lead to cessation attempts among smokers with different levels of self-efficacy to quit, of response efficacy beliefs, or of trait reactance against attempts to control their behavior.