PURPOSE: Controversy persists over whether cancer risk is increased in communities surrounding oil fields, especially in the Oriente region of Ecuador. This ecologic study uses quantitative exposure data, updated mortality data, and improved statistical methods to study the impact of oil exploration and production activities on cancer mortality rates in the Oriente. METHODS: Cancer mortality rates in the Oriente in 1990 through 2010 were compared between seven cantons with active oil exploration and production as of 1990 and thirteen cantons with little or no such activities. Poisson regression was used to estimate mortality rate ratios (RRs) adjusted for age and sex. In a two-stage analysis, canton-specific log-RRs were regressed against quantitative estimates of cumulative barrels of oil produced and well-years per canton, adjusting for canton-level demographic and socioeconomic factors. RESULTS: Overall and site-specific cancer mortality rates were comparable between oil-producing and non-oil-producing cantons. For overall cancer mortality in males and females combined, the RR comparing oil-producing to non-oil-producing cantons was 0.85 [95 % confidence interval (CI) 0.72-1.00]. For leukemia mortality, the corresponding RR was 0.80 (95 % CI 0.57-1.13). Results also revealed no excess of mortality from acute non-lymphocytic, myeloid, or childhood leukemia. Standardized mortality ratios were consistent with RRs. Canton-specific RRs showed no pattern in relation to oil production volume or well-years. CONCLUSIONS: Results from this first ecologic study to incorporate quantitative measures of oil exploration and production showed no association between the extent of these activities and cancer mortality, including from cancers associated with benzene exposure.