Traditionally, optical fiber nonlinearity is considered a limiting factor for transmission systems. Nevertheless, from a system design perspective this nonlinearity can be exploited to minimize the impact of uncertainty on the system performance. A consequence of this is that it becomes beneficial to consider the uncertainty at the design stage, resulting in a probabilistic design, rather than conventional design approaches whereby uncertainty is added by way of system margins to a deterministic design. In this paper, we conduct extensive experimental measurements to quantify the impact of uncertainty for a multispan wavelength division multiplexed system transmitting 100 GbE or 200 GbE as dual polarization quadrature phase-shift keying (QPSK) or 16 quadrature amplitude modulation (16QAM), respectively. The impact of uncertainty in the power launched into a span is assessed for a 10 × 80 km link. For dual polarization (DP)-QPSK, the intralink power deviation with the probabilistic design with 100% reliability is ±1.3 dB falling to 99% reliability with ±1.6 dB. In contrast, for DP-16QAM maximum deviation for 100% reliability is ±0.5 dB falling to 99% for ±0.6 dB. Following this, we consider the interplay between polarization dependent loss (PDL) and fiber nonlinearity over an 8 × 80 km system again for both DP-QPSK and DP-16QAM. A system Q variation of less than 0.15 dB due to the interaction between PDL and fiber nonlinearity is observed for 99.9% of examined PDL values for DP-QPSK and DP-16QAM, thereby allowing the two effects to be considered separately. ; This research was supported by a Ciena University collaborative research grant. The work of H.-M. Chin was supported in part by a Ph.D. studentship from Ciena and in part by EU ICONE Project under Grant #608099. The work of S. J. Savory was supported by a Senior Research Fellowship from the RAEng/The Leverhulme Trust.