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Karloff Lagarde's biggest year was 1964, when he etched his name in history as holding three titles at once, beating El Santo himself to do it. Lagarde captured the Mexican National Middleweight Championship on April 11, 1963 and held all three titles for two months. Lagarde was voted wrestler of the year in the magazines.

Lagarde's success opened doors for other members of his family: his son Karloff Lagarde Jr. and his brother Angel Negro enjoyed lucha libre careers. Lagarde won other titles, including the National Tag Team Championship with his real life friend Rene Guajardo, and they often teamed during their careers.