Greater levels of psychological well-being are associated with reduced disease and mortality risk, and lifestyle habits may be potential mechanisms underlying these relationships. Prospective studies show that positive psychological factors enhance the likelihood of adopting specific health behaviors; yet, whether they promote the adoption of multiple healthy behaviors, which can have a multiplicative effect on disease and mortality risk compared to individual behaviors, is unknown. We investigated whether happiness and optimism were related to a healthy lifestyle (characterized by multiple health behaviors) over 10-22 years of follow-up; we also explored bidirectional associations, assessing if a healthy lifestyle at baseline was related to greater likelihood of experiencing higher happiness and optimism over time. Women reported levels of happiness in 1992 (N = 52,133) and optimism in 2004 (N = 36,802). Health-related behaviors (physical activity, body mass index, diet, alcohol and tobacco consumption) were self-reported and combined into a lifestyle score, every four years from baseline until 2014. Multivariable generalized estimating equations with a Poisson distribution were used. Women with moderate and higher (versus lower) happiness levels were more likely to report sustaining healthy lifestyles (RR = 1.18, CI = 1.11-1.25; RR = 1.39, CI = 1.32-1.46, respectively). In secondary analyses, the magnitude of the inverse association was somewhat smaller (likelihood of sustaining higher happiness levels for baseline healthy versus unhealthy lifestyle, RR = 1.11, CI = 1.10-1.12). Results were similar when considering optimism as the exposure and in other secondary analyses (e.g., across individual habits). While bidirectional associations are apparent, these findings suggest pursuing happiness and optimism as modifiable determinants of lifestyle deserves further consideration.