Adult second language (L2) learners often experience difficulty with novel L2 phonological contrasts, limiting their ability to establish contrastive lexical representations of L2 words. It has been demonstrated that the availability of orthographic input (OI), and variables interacting with OI, can shape the inferences learners make about L2 words' phonological forms. The present dissertation focuses on grapheme familiarity and congruence, in addition to L2 experience and the effect of instruction, in the case of native English speakers learning L2 Russian(-like) words presented in Cyrillic. Few studies have directly investigated effects of grapheme familiarity and congruence on phono-lexical acquisition simultaneously, systematically investigated the variables' effects on naive and experienced L2 learners, or investigated how explicit intervention can mediate OI effects. The present dissertation addresses these gaps in our understanding. The two studies in this dissertation employed the artificial L2 lexicon paradigm. Taken together, the results indicate the following: (i) native language orthographic interference effects are robust in L2 word learning, especially when grapheme-phoneme correspondences are incongruent (unfamiliar and congruent stimuli did not cause difficulty); (ii) experience with the Russian language mediates this interference, with advanced learners performing near ceiling on all stimuli types and naive learners performing least accurately; and (iii) naive learners do not seem to benefit from textual enhancement and instruction prior to word learning in an experiment. The results of the present dissertation suggest that more research is needed to address the challenges associated with the interference effects of OI in L2 acquisition. [The dissertation citations contained here are published with the permission of ProQuest LLC. Further reproduction is prohibited without permission. Copies of dissertations may be obtained by Telephone (800) 1-800-521-0600. Web page: http://bibliotheek.ehb.be:2222/en-US/products/dissertations/individuals.shtml.]