Crude tankers emit volatile organic compounds (VOCs) that are highly flammable and hazardous to human health and the environment. In light of these hazards, an international law has been enforced to regulate obligatory implementation of VOC management plans on board crude oil tankers. There are few thorough investigations that have simultaneously considered the various aspects of VOC recovery from the loading of crude oil into oil tankers. The current study investigated a compression-assisted refrigeration condensation system for VOC recovery during crude oil loading operations. System performance and the profit with different operation conditions showed rather a complicated relation than just a trade-off. The optimum process configuration and the ideal operational conditions of compression pressure and refrigeration temperature were determined through process simulation combined multi-objective optimization based on economic and environmental cost-benefit assessments. For the sake of safety, a risk assessment is performed to obtain information needed to make decisions about the safe design of a VOC recovery process. A hazard and operability analysis (HAZOP) is conducted to identify plausible hazardous scenarios. A layer of protection analysis (LOPA) is subsequently conducted to overcome the qualitative nature of HAZOP. The current mitigation is estimated by multiplying the initiating cause likelihoods by the PFDs for the applicable IPLs and adjustment values. The estimated current mitigation is then compared to a risk acceptance criterion to make recommendations for design improvements to further reduce risks to an acceptable level.