Guidelines stress the importance of the simultaneous management of multiple cardiovascular risk factors. This can in part be achieved by coadministration of lipid‐lowering and antihypertensive treatments. Potential pharmacodynamic interaction between drugs should be investigated as part of developing single‐pill combinations. The Respond trial assessed whether combining amlodipine to treat hypertension and atorvastatin to treat dyslipidemia affected the action of either monotherapy. A total of 1660 hypertensive patients with dyslipidemia received 1 of 15 combinations of amlodipine (placebo, 5, or 10 mg) and atorvastatin (placebo, 10, 20, 40, or 80 mg) in a 3 × 5 factorial randomized, placebo‐controlled design. At 8 weeks, combination‐treated patients experienced dose‐related and statistically significant reductions in systolic blood pressure, low‐density lipoprotein cholesterol, and Framingham risk score. Overall, coadministered atorvastatin and amlodipine was well tolerated and without adverse pharmacodynamic interaction; combination treatment did not affect the low‐density lipoprotein cholesterol‐lowering efficacy and safety of atorvastatin, or the systolic blood pressure‐lowering efficacy and safety of amlodipine.