The Heaviness of Smoking Index (HSI) is the measure of dependence most strongly predictive of relapse. However, recent research suggests it may not be predictive of longer-term relapse. Our aim was to examine its predictive power over the first 2 years after quitting and explore whether use of stop-smoking medications is a moderator. Data (n = 7,093) came from the first 7 waves (2002-2009) of the International Tobacco Control Four-Country Survey, an annual cohort survey of smokers in Canada, the United States, the United Kingdom, and Australia. HSI and its 2 components (cigarettes per day [CPD] and time to first cigarette [TTFC]) were used to predict smoking relapse risk in the 2 years after the start of a quit attempt. Scores on HSI and its components all strongly predicted relapse, but there was an interaction with time (p < .001). These measures were strong predictors of relapse within the first week of quitting (hazard ratios [HR] = 1.17, 1.24, and 1.30 for HSI, CPD, and TTFC, respectively; all p < .001), less predictive of relapse occurring between 1 week and 1 month, and not clearly predictive beyond 1 month. Among those using medication to quit, hazard ratio for HSI (HR = 1.11, p < .001) was significantly lower than for those not using (HR = 1.24, p < .001) in the first week but not beyond. HSI and its 2 components are strong predictors of short-term smoking relapse, but they rapidly lose predictive power over the first weeks of an attempt, becoming marginally significant at around 1 month and not clearly predictive beyond then.