An artificially pigmented retinal pigment epithelial (RPE) cell model was used to study the damage rates for exposure to 1, 10, 100, and 1,000 230-μs laser pulses at 532 nm, at two different concentrations of melanosome particles (MPs) per cell. Multiple pulses were delivered at pulse repetition rates of 50 and 99 pulses per second. Standard fluorescence viability indicator dyes and the method of microthermography were used to assess damage and thermal responses, respectively. Although frame rate during microthermography was more than five times slower than the duration of laser pulses, thermal information was useful in refining the BTEC computational model for simulating high-resolution thermal responses by the pigmented cells. When we temporally sampled the thermal model output at a rate similar to our microthermography, the resulting thermal profiles for multiple pulses resembled the thermal experimental profiles. Complementary to the thermal simulations, our computer-generated thresholds were in good agreement with the in vitro data. Findings are examined within the context of common exposure limit definitions in the national and international laser safety standards.