Little is known about the magnitude and duration of mood responses to daily negative events as a function of gender, history of mood disorder, and current substance use. Using computerized ambulatory monitoring techniques, perceived negativity of minor daily events and state affect were prospectively examined every 3 h on average for a 7-day period. Event negativity was associated with depressed mood for 6–9 h following event occurrence, and was associated with happy mood for 3–6 h. Gender and substance use moderated the relationship between event negativity and mood states concurrently, and remained influential for approximately 3 h following the event. History of mood disorder did not moderate any within- or across-day relationships between event negativity and mood. No evidence was found for mood uplifts following daily events in either within- or across-day analyses. The findings are discussed relative to assessment timing in investigations of vulnerability-stress theories.