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Insights into combination HIV prevention (CHP) strategies to reduce HIV incidence among midlife and older adult men who have sex with men (MSM) are limited. The current study is a secondary data analysis evaluating CHP in a sample of sexually active midlife and older adult MSM (N = 566) from the Multicenter AIDS Cohort Study Healthy Aging Substudy. Stratified by HIV serostatus, we used latent class analyses to identify CHP classes based on self-reported sociobehavioral and biobehavioral prevention strategies that participants and their male partners used in the prior 6 months. We identified three CHP classes among men living without HIV (MLWOH), including the following: high CHP overall (43.0%), high anal sex abstention (15.0%), and low prevention overall (42.0%). Among men living with HIV (MLWH), we identified four CHP classes, including the following: high CHP overall (20.9%), high CHP/low condom use (27.1%), high condom reliance (22.3%), and low prevention overall (29.7%). There were small differences by sociodemographic characteristics and sexual behavior practices between the classes; however, poppers use was often linked to being in high CHP groups. Our findings support that CHP is not one-size-fits-all for midlife and older adult MSM. There remains a need to scale up clinical providers' sexual health communication practices to assist midlife and older MSM incorporate prevention strategies, particularly biobehavioral prevention strategies that align with their patients' lived experiences. [ABSTRACT FROM AUTHOR]