Background: Training in responsible conduct of research and human subjects protections (RCR/HSP) is seldom included in postgraduate medical education in low-and middle-income (LMIC) countries despite requirements that residents undertake research projects. Investigators introduced a Spanish-language training program in RCR/HSP for surgical residents in Guatemala using “off-the-shelf” on-line materials, developed a new in-person curriculum specific to the local context, and compared the two teaching modalities with the aim of generating recommendations to improve resident training. Methods: In 2018, surgical residents in three large urban hospitals in Guatemala City completed two on-line programs in RCR/HSP as well as pre- and post-training assessments. Residents in the intervention arm also completed seven weeks of in-person training. Assessments tested awareness of key concepts in the on-line courses with particular attention to international and Guatemalan research regulations. Group differences in matched (pre- and post-) mean scores were analyzed using t-tests to determine gains by study arm assignment. Results: Of the 160 surgical residents, 140 completed pre- and post-training assessments and were included in the analytic sample. Overall mean scores improved from 52.7 to 58.7 points out of 100.The differences in gains between the two arms were very small and there was insufficient statistical power to detect significance. Trainees completing in-person training reported greater confidence in recognizing ethical issues, understanding the legal and ethical requirements for research, and identifying, reporting and avoiding scientific misconduct than trainees who completed on-line training only. Conclusion: Differences in gains in RCR/HSP knowledge and self-efficacy between trainees completing on-line training only and those completing in-person as well as on-line training are too modest to preference one mode of instruction over another in this setting. Given the limited availability of RCR/HSP faculty, financial resources, and time in the surgical training schedule, however, the investigators recommend that academic authorities in Guatemala consider on-line training programs in RCR/HSP in all surgical residency programs as an affordable and scalable strategy to build ethical research skills in its surgical workforce.