Background Previous studies suggest that the relationship between genetic risk and depression may be moderated by stressful life events (SLEs). The goal of this study was to assess whether SLEs moderate the association between polygenic risk of Major Depressive Disorder (MDD) and depressive symptoms in older adults. Methods We used logistic and negative binomial regressions to assess the associations between polygenic risk, SLEs and depressive symptoms in a sample of 8,761 participants from the Health and Retirement Study (HRS). Polygenic scores were derived from the Psychiatric Genomics Consortium (PGC) genome-wide association study (GWAS) of MDD. SLEs were operationalized as a dichotomous variable indicating whether participants had experienced at least 1 stressful event during the previous two years. Depressive symptoms were measured using an 8-item CES-D subscale and operationalized as both a dichotomous and a count variable. Results The odds of reporting ≥ 4 depressive symptoms were over twice as high among individuals who experienced at least one SLE (OR = 2.19, 95% CI = [1.86, 2.58]). Polygenic scores were significantly associated with depressive symptoms (β = .21, p = <.0001), although the variance explained was modest (Pseudo r2 = .0095). None of the interaction terms for polygenic scores and SLEs were statistically significant. Conclusions Polygenic risk and SLEs are robust, independent predictors of depressive symptoms in older adults. Consistent with an additive model, we found no evidence that SLEs moderated the association between common variant polygenic risk and depressive symptoms.