Smoking is associated with particular moods and activities, but it is not known whether there are individual differences in these associations and whether these differences are associated with success in smoking cessation. We assessed such associations using ecological momentary assessment: real-world, real-time data, collected by palm-top computer. Two hundred and fourteen smokers participating in a smoking cessation study provided data during ad lib smoking at baseline. Participants recorded moods and activities each time they smoked and, for comparison, at randomly selected non-smoking occasions. Situational associations with smoking were captured by examining the associations between smoking and antecedents considered relevant to lapse risk: negative affect (NA), arousal, socializing with others, the presence of others smoking, and consumption of coffee and alcohol. The associations varied across participants, confirming individual differences in situational smoking associations. Survival analyses revealed that only the NA pattern predicted first lapse. The effect was only seen in EMA assessments of NA smoking, and was not captured by questionnaire measures of negative affect smoking, which did not predict lapse risk. Moreover, the effect was not mediated by nicotine dependence.