Background: Mental health nursing simulation using various modalities can be useful in increasing student confidence, satisfaction, knowledge, and communication skills. Studies comparing the benefits of mental health nursing simulation using standardized patients versus mannequins are scarce. Aims: The purpose of this study was to explore differences in knowledge, clinical learning, clinical reasoning, communication, confidence, and learner satisfaction when conducting mental health nursing simulation with standardized patients compared to mannequins. Methods: A convenience sample of 178 senior level baccalaureate nursing students enrolled in the mental health nursing course participated in this study. Of the total sample, 41.6% ( n = 74) participated in high-fidelity mannequin simulation and 58.4% ( n = 104) in standardized patient simulation. Measures included a knowledge assessment, Satisfaction with Simulation Experience Scale (SSE), and a simulation evaluation survey. Results: While knowledge levels increased regardless of simulation modality, clinical reasoning, clinical learning, communication, realism, and overall rating of the simulation experience were significantly higher among participants in standardized patient simulation compared to mannequins. Conclusions: Mental health simulations can be a useful learning tool for engaging in mental health scenarios in a safe simulated learning environment. While both mannequins and standardized patient modalities are helpful in increasing mental health nursing knowledge, standardized patient simulation has a greater impact on several other aspects including clinical reasoning and communication. Future multisite studies with larger samples are needed, including a wider variety of mental health scenarios.