BACKGROUND: The potential effects of dietary oxalate (Ox) intake on cardio-renal function have remained unestablished. We evaluated the effect of usual Ox intake and its interaction with dietary calcium (Ca) on incident hypertension (HTN) and chronic kidney disease (CKD). METHODS: Adult men and women, free of HTN and CKD at baseline (2006-2008), were recruited. Dietary intakes were assessed using a validated food frequency questionnaire, and the outcomes were documented up to 2014-2017. Multivariate Cox proportional hazard regression models were used to estimate the development of HTN and CKD in relation to Ox intakes. Repeated-measures generalized estimating equation (GEE) linear regression models were used to assess possible effect of Ox-intake on the estimated glomerular filtration rate (eGFR) and blood pressure levels over eight years. RESULTS: Dietary Ox intakes were positively associated with incident CKD (HR = 2.59, 95% CI = 1.46-4.64) and HTN (HR = 1.79, 95% CI = 1.05-3.04). Compared to high-Ca consumers, subjects who had lower Ca intakes (< 990 vs. 1580 mg/d) had a higher incidence of CKD and HTN (HR = 2.43, 95% CI = 1.06-5.55, and HR = 1.72, 95% CI = 0.76-3.78). Participants with higher intakes of Ox (> 220 vs. < 150 mg/d) had lower eGFR values (75.3, 95% CI = 75.0-76.5 vs. 77.3, 95% CI = 76.6-78.1 mL/min/1.73m, P = 0.004) and higher SBP levels (112, 95% CI = 111-113 vs. 109, 95% CI = 108-110 mmHg, P = 0.007) overtime. CONCLUSION: Higher dietary Ox intake may increase the risk of HTN and CKD. The relation between dietary Ox and risk of HTN and CKD seems to be varied by Ca intake, and subjects with lower Ca intakes may be more burdened by excessive amounts of dietary Ox.