In 1832-33, Ripley commanded the Federal forces in Charleston harbor at the time of the nullification movement in South Carolina. He was promoted captain (1832), major of ordnance (1838), and brevet lieutenant colonel (1848). In 1854 he was transferred to the Watertown Arsenal as commandant of the facility.
With the outbreak of the Civil War in early 1861, Ripley was commissioned brigadier general and appointed chief of ordnance of the army. As the Federal forces had then no heavy rifled cannon, he immediately ordered the conversion of old smoothbores and the manufacture of Parrott guns.
At the same time, Ripley refused to authorize the purchase of additional stocks of rifle-muskets for infantry use. The decision was based in the large existing stocks of smoothbore muskets in U.S. arsenals, which he argued could be re-rifled in the same manner as the Parrot guns (an assertion which proved incorrect). He also adamantly opposed the introduction of breech-loading repeating rifles, on the basis that they would encourage poor fire discipline and waste ammunition.
Many historians have since decried this decision, arguing the lack of modern arms on the Union side, at a time when the Confederates were buying them in large numbers from France and the United Kingdom, lengthened the conflict by as much as two years. Others, however, counter that given the poor logistics of the Union armies at the outbreak of the war, the increased supply train needed to maintain the improved rates of fire would have bogged down the armies and made maneuver impossible (a situation which did indeed later contribute to the development of trench warfare in World War I). It is also argued that fouling due to black powder residue would have made it impossible to maintain such high rates of fire under field conditions with the rifles of the time. Individual units would later purchase such weapons privately, and they were used to considerable effect, but did indeed present problems in extended firefights; these units are not known to have had any trouble maintaining their ammunition supplies.
From 1863 to the year of his death, he was inspector of fortifications on the New England coast, having retired from active service. In 1865 he had been brevetted major general in the regular army. He died in Hartford, Connecticut, where he is buried.