Reliable malaria related mortality data is important for planning appropriate interventions. However, there is scarce information on the pattern of malaria related mortality in epidemic prone districts of Tanzania. This study was carried out to determine malaria related mortality and establish its trend change over time in both epidemic and non-epidemic areas of Muleba District of north-western Tanzania. A verbal autopsy survey was conducted to obtain data on all deaths of individuals who died in six randomly selected villages from 1997 to 2006. Relatives of the deceased were interviewed using a standardized questionnaire. Communicable diseases accounted for about two thirds (61.9%) of deaths among ≥5 years individuals and 84.8% in ≤5 years. Non-communicable diseases accounted for 28.9% and 14.1% deaths in ≥5 years and ≤5 years, respectively. Malaria was the leading cause of deaths in all age groups (40.3%) and among children <5 years (73.8%). Infants accounted for about two third (64.5%) of all malaria related deaths in children <5 years. Peak of malaria proportional mortality was highest during malaria epidemics. Most of the malaria-related deaths in this group were among 1-12 months (64.5%) followed by 13-24 months (20.9%), and 25-59months (14.8%). Cerebral malaria accounted for 18.9% (N=32) of death related to malaria in all age groups; 12.1% (17/141) were in under-five, 42.9% (6/14) were in 5-14 years and 64.3% (9/14) in 15-70 years old. More than half of malaria related deaths (61.0%) in <5 years children were associated with severe anaemia followed by diarrhoeal disease (24.1%), cerebral malaria (12.5%) and respiratory infection (8.5%) as common conditions. The majority of the deceased caretakers first sought treatment at health facilities within 24hr of the onset of illness. Significantly a higher proportion of caretakers of the underfives in the epidemic area sought treatment within 24hr than in non-epidemic area (39.3% vs. 18.5%; P=0.0385). In conclusion, malaria accounts for majority of deaths in Muleba district, with substantial proportion being attributed to malaria epidemics. _______________________________________________________________________________________