Background: The Hospital Survey on Patient Safety Culture (HSOPSC) is widely utilized in multiple languages across the world. Despite culture and language variations, research studies from Latin America use the Spanish language HSOPSC validated for Spain and the United States. Yet, these studies fail to report the translation method, cultural adaptation process, and the equivalence assessment strategy. As such, the psychometric properties of the HSOPSC are not well demonstrated for cross-cultural research in Latin America, including Peru. The purpose of this study was to develop a target-language HSOPSC for cross-cultural research in Peru that asks the same questions, in the same manner, with the same intended meaning, as the source instrument. Methods: This study used a mixed-methods approach adapted from the translation guideline recommended by Agency for Healthcare Research and Quality. The 3-phase, 7-step process incorporated translation techniques, pilot testing, cognitive interviews, clinical participant review, and subject matter expert evaluation. Results: The instrument was translated and evaluated in 3 rounds of cognitive interview (CI). There were 37 problem items identified in round 1 (14 clarity, 12 cultural, 11 mixed); and resolved to 4 problems by round 3. The pilot-testing language clarity inter-rater reliability was S-CVI/Avg = 0.97 and S-CVI/UA = 0.86; and S-CVI/Avg = 0.96 and S-CVI/UA = 0.83 for cultural relevance. Subject matter expert agreement in matching items to the correct dimensions was substantially equivalent (Kappa = 0.72). Only 1 of 12 dimensions had a low Kappa (0.39), borderline fair to moderate. The remaining dimensions performed well (7 = almost perfect, 2 = substantial, and 2 = moderate).